Pharmacokinetics and Pharmacodynamics of Lansoprazole/Sodium Bicarbonate Immediate-release Capsules in Healthy Chinese Subjects: An Open, Randomized, Controlled, Crossover, Single-, and Multiple-dose Trial.

Proton pump inhibitors (PPIs) differ in onset of action and bioavailability. This trial was conducted to investigate the pharmacokinetics and pharmacodynamics of an immediate-release capsule formulation containing lansoprazole 30 mg and sodium bicarbonate 1100 mg (T preparation) in healthy Chinese subjects. This was an open, single-center, randomized, single and multiple oral doses, and two-period crossover study in 30 healthy subjects. After single- and multiple-dose oral administration, blood samples were obtained and lansoprazole concentration in serum was measured for pharmacokinetic analysis. Meanwhile, the intragastric pH was monitored continuously to evaluate the pharmacodynamics of the investigational drugs. The Tmax of the T preparation was 0.5 hours, while the Tmax of the R preparation was 1.5 hours after multiple doses, which indicated that the absorption speed of the T preparation was significantly faster than that of the R preparation. The same characteristics also existed after single-dose administration. The area under the curve (AUC)ss of the T preparation was bio-equivalent to that of the R preparation under steady state. The time percentage of intragastric pH > 4.0 for the T preparation was higher than that of the R preparation after 1 hour for both single- and multiple-dose. It suggested compared with R preparation, the time percentage of intragastric pH > 4.0 met the criteria for superiority after 1 hour administration for the T preparation. In addition, no serious adverse events occurred in this study. Across this study, the T preparation was better than the R preparation at improving drug absorption and increasing intragastric pH, and had a favorable safety profile.

Is Individualization of Sodium Bicarbonate Ingestion Based on Time to Peak Necessary?

PURPOSE: To describe the reliability of blood bicarbonate pharmacokinetics in response to sodium bicarbonate (SB) supplementation across multiple occasions and assess, using putative thresholds, whether individual variation indicated a need for individualized ingestion timings. METHODS: Thirteen men (age 27 ± 5 yr; body mass [BM], 77.4 ± 10.5 kg; height, 1.75 ± 0.06 m) ingested 0.3 g·kg BM SB in gelatine capsules on three occasions. One hour after a standardized meal, venous blood was obtained before and every 10 min after ingestion for 3 h, then every 20 min for a further hour. Time to peak (Tmax), absolute peak (Cmax), absolute peak change ([INCREMENT]Cmax), and area under the curve were analyzed using mixed models, intraclass correlation coefficient, coefficient of variation and typical error. Individual variation in pharmacokinetic responses was assessed using Bayesian simulation with multilevel models with random intercepts. RESULTS: No significant differences between sessions were shown for blood bicarbonate regarding Cmax, [INCREMENT]Cmax or area under the curve (P > 0.05), although Tmax occurred earlier in SB2 (127 ± 36 min) than in SB1 (169 ± 54 min, P = 0.0088) and SB3 (159 ± 42 min, P = 0.05). Intraclass correlation coefficient, coefficient of variation, and typical error showed moderate to poor reliability. Bayesian modeling estimated that >80% of individuals from the population experience elevated blood bicarbonate levels above +5 mmol·L between 75 and 240 min after ingestion, and between 90 and 225 min above +6 mmol·L. CONCLUSIONS: Assessing SB supplementation using discrete values showed only moderate reliability at the group level, and poor reliability at the individual level, whereas Tmax was not reproducible. However, when analyzed as modeled curves, a 0.3-g·kg BM dose was shown to create a long-lasting window of ergogenic potential, challenging the notion that SB ingestion individualized to time-to-peak is a necessary strategy, at least when SB is ingested in capsules.

Sodium Fate after Sodium Bicarbonate Infusion: Influence of Altered Acid-Base Status.

BACKGROUND: We have previously investigated the fate of administered bicarbonate infused as a hypertonic solution in animals with each of the 4 chronic acid-base disorders. Those studies did not address the fate of sodium, the coadministered cation. METHODS: We examined baseline total body water (TBW), Na+ space, HCO3- space, and urinary sodium and bicarbonate excretion after acute hypertonic NaHCO3 infusion (1-N solution, 5 mmol/kg body weight) in dogs with each of the 4 chronic acid-base disorders. Observations were made at 30, 60, and 90 min postinfusion. Retained sodium that remains osmotically active distributes in an apparent space that approximates TBW. Na+ space that exceeds TBW uncovers nonosmotic sodium storage. RESULTS: Na+ space approximated TBW at all times in normal and hyperbicarbonatemic animals (metabolic alkalosis and respiratory acidosis), but exceeded TBW by ~30% in hypobicarbonatemic animals (metabolic acidosis and respiratory alkalosis). Such osmotic inactivation was detected at 30 min and remained stable. The pooled data revealed that Na+ space corrected for TBW was independent of the initial blood pH but correlated with initial extracellular bicarbonate concentration (y = -0.01x + 1.4, p= 0.002). The fate of administered sodium and bicarbonate (internal distribution and urinary excretion) was closely linked. CONCLUSIONS: This study demonstrates that hypobicarbonatemic animals have a Na+ space that exceeds TBW after an acute infusion of hypertonic NaHCO3 indicating osmotic inactivation of a fraction of retained sodium. In addition to an expanded Na+ space, these animals have a larger HCO3- space compared with hyperbicarbonatemic animals. Both phenomena appear to reflect the wider range of titration of nonbicarbonate buffers (Δ pH) occurring during NaHCO3- loading whenever initial [HCO3-]e is low. The data indicate that the fate of administered bicarbonate drives the internal distribution and the external disposal of sodium, the co-administered cation, and is responsible for the early, but non-progressive, osmotic inactivation of a fraction of the retained sodium.

Enteric-Coated Sodium Bicarbonate Attenuates Gastrointestinal Side-Effects.

Enteric-formulated capsules can mitigate gastrointestinal (GI) side effects following sodium bicarbonate (NaHCO3) ingestion; however, it remains unclear how encapsulation alters postingestion symptoms and acid-base balance. The current study aimed to identify the optimal ingestion form to mitigate GI distress following NaHCO3 ingestion. Trained males (n = 14) ingested 300 mg/kg body mass of NaHCO3 in gelatin (GEL), delayed-release (DEL), and enteric-coated (ENT) capsules or a placebo in a randomized cross-over design. Blood bicarbonate anion concentration, potential hydrogen, and GI symptoms were measured pre- and postingestion for 3 hr. Fewer GI symptoms were reported with ENT NaHCO3 than with GEL (p = .012), but not with DEL (p = .106) in the postingestion phase. Symptom severity decreased with DEL (4.6 ± 2.8 arbitrary units) compared with GEL (7.0 ± 2.6 arbitrary units; p = .001) and was lower with ENT (2.8 ± 1.9 arbitrary units) compared with both GEL (p < .0005) and DEL (p = .044) NaHCO3. Blood bicarbonate anion concentration increased in all NaHCO3 conditions compared with the placebo (p < .0005), although this was lower with ENT than with GEL (p = .001) and DEL (p < .0005) NaHCO3. Changes in blood potential hydrogen were reduced with ENT compared with GEL (p = .047) and DEL (p = .047) NaHCO3, with no other differences between the conditions. Ingestion of ENT NaHCO3 attenuates GI disturbances for up to 3 hr postingestion. Therefore, ENT ingestion forms may be favorable for those who report GI disturbances with NaHCO3 supplementation or for those who have previously been deterred from its use altogether.

A Randomized Trial Comparing the Safety, Adherence, and Pharmacodynamics Profiles of Two Doses of Sodium Bicarbonate in CKD: the BASE Pilot Trial.

BACKGROUND: Oral sodium bicarbonate (NaHCO3) may preserve kidney function in CKD, even if initiated when serum bicarbonate concentration is normal. Adequately powered trials testing this hypothesis have not been conducted, partly because the best dose for testing is unknown. METHODS: This multicenter pilot trial assessed the safety, tolerability, adherence, and pharmacodynamics of two doses of NaHCO3 over 28 weeks in adults with eGFR 20-44 or 45-59 ml/min per 1.73 m2 with urinary albumin/creatinine (ACR) ≥50 mg/g and serum bicarbonate 20-28 meq/L. We randomly assigned 194 participants from ten clinical sites to receive higher-dose (HD-NaHCO3; 0.8 meq/kg of lean body wt per day; n=90) or lower-dose (LD-NaHCO3; 0.5 meq/kg of lean body wt per day; n=52) NaHCO3 or matching placebo (n=52). The dose was adjusted depending on side effects. The prescribed dose at week 28 was the primary outcome; a dose was considered acceptable for a full-scale trial if ≥67% of participants were on full-dose and ≥80% were on ≥25% of the per-protocol dose. RESULTS: Mean±SD baseline eGFR was 36±9 ml/min per 1.73 m2, serum bicarbonate was 24±2 meq/L, and median (IQR) ACR was 181 (25-745) mg/g. Both doses were well tolerated without significant changes in BP, weight, or serum potassium. The proportions of adverse events and hospitalizations were similar across the groups. Consequently, 87% in HD-NaHCO3, 96% in LD-NaHCO3, and 87% in placebo were on full dose at week 28; and 91% in HD-NaHCO3, 98% in LD-NaHCO3, and 92% in placebo were on ≥25% of the per-protocol dose. Mean urinary ammonium excretion was 25% lower and serum bicarbonate concentration was 1.3 meq/L higher in HD-NaHCO3 compared with LD-NaHCO3 at week 28. However, mean ACR increased by 12% in the lower-dose group and 30% in the higher-dose group. CONCLUSIONS: Both NaHCO3 doses were well tolerated over 28 weeks with no significant difference in adverse events or hospitalization compared with placebo. The higher dose lowered urinary ammonium excretion and increased serum bicarbonate more than the lower dose but was associated with a greater increase in ACR. The higher 0.8 meq/kg of lean body wt per day dose of NaHCO3 may be a reasonable choice for future trials.

The safety, pharmacodynamics, and pharmacokinetics of immediate-release formulation containing esomeprazole 20 mg/sodium bicarbonate 800 mg in healthy adult male.

BACKGROUND: Esomeprazole is the most effective treatment for acid-related disorders and is widely used with enteric coating due to rapid degradation in the acidic environment. However, the enteric-coated formulation delays absorption and onset of action. To overcome this limitation, an immediate-release formulation containing esomeprazole 20 mg and sodium bicarbonate 800 mg (IR-ESO) was developed. PURPOSE: To evaluate the safety, pharmacokinetics (PK), and pharmacodynamics of IR-ESO compared to those of esomeprazole 20 mg (ESO). METHODS: A randomized, open-label, multiple-dose, two-treatment, two-sequence crossover study was conducted in 40 healthy male subjects. Subjects received either IR-ESO or ESO for 7 days. After single and multiple dosing, blood samples were collected for PK analysis, and intragastric pH was assessed by 24-hr pH monitoring. RESULTS: Plasma esomeprazole exposure of IR-ESO was similar to that of ESO after single and multiple dosing. Time to peak concentration of IR-ESO (0.50-0.75 hr) was shorter than that of ESO (1.25-1.50 hr). Percentage changes in 24-hr integrated gastric acidity from baseline for IR-ESO were similar to those for ESO. In addition, mean time to maintain gastric pH >4 for 24 hr was similar for both drugs (IR-ESO 55.5-69.9% vs ESO 56.8-70.2%). Evaluation of time to first reach pH 4 after dosing indicated that IR-ESO showed a faster onset than ESO. All subjects found the drug tolerable, and there were no significant differences in adverse events between two drugs. CONCLUSION: This study showed that IR-ESO produced a rapid, safe and sustained gastric acid suppression (ClinicalTrials.gov: NCT03211143).

Sodium bicarbonate nanoparticles modulate the tumor pH and enhance the cellular uptake of doxorubicin.

Acidic pH in the tumor microenvironment is associated with cancer metabolism and creates a physiological barrier that prevents from drugs to penetrate cells. Specifically, ionizable weak-base drugs, such as doxorubicin, freely permeate membranes in their uncharged form, however, in the acidic tumor microenvironment these drugs become charged and their cellular permeability is retarded. In this study, 100-nm liposomes loaded with sodium bicarbonate were used as adjuvants to elevate the tumor pH. Combined treatment of triple-negative breast cancer cells (4T1) with doxorubicin and sodium-bicarbonate enhanced drug uptake and increased its anti-cancer activity. In vivo, mice bearing orthotropic 4T1 breast cancer tumors were administered either liposomal or free bicarbonate intravenously. 3.7 ±â€¯0.3% of the injected liposomal dose was detected in the tumor after twenty-four hours, compared to 0.17% ±â€¯0.04% in the group injected free non-liposomal bicarbonate, a 21-fold increase. Analyzing nanoparticle biodistribution within the tumor tissue revealed that 93% of the PEGylated liposomes accumulated in the extracellular matrix, while 7% were detected intracellularly. Mice administered bicarbonate-loaded liposomes reached an intra-tumor pH value of 7.38 ±â€¯0.04. Treating tumors with liposomal bicarbonate combined with a sub-therapeutic dose of doxorubicin achieved an improved therapeutic outcome, compared to mice treated with doxorubicin or bicarbonate alone. Interestingly, analysis of the tumor microenvironment demonstrated an increase in immune cell' population (T-cell, B-cell and macrophages) in tumors treated with liposomal bicarbonate. This study demonstrates that targeting metabolic adjuvants with nanoparticles to the tumor microenvironment can enhance anticancer drug activity and improve treatment.

Is Bypassing the Stomach a Means to Optimize Sodium Bicarbonate Supplementation? A Case Study With a Postbariatric Surgery Individual.

Sodium bicarbonate (SB) is an ergogenic supplement shown to improve high-intensity exercise via increased blood bicarbonate buffering. Substantial amounts of the ingested bicarbonate are neutralized in the stomach. Bariatric surgery results in a small gastric pouch which dramatically reduces exposure time of any ingested food in the stomach. The aim of this study was to examine the pharmacokinetics of orally ingested SB in a postgastric bypass individual to determine the magnitude of changes in blood bicarbonate and associated side effects. We hypothesized that SB supplementation in a gastric bypass model would result in greater blood bicarbonate increases and fewer side effects than in healthy individuals due to minimal bicarbonate losses in the stomach. One postbariatric male ingested 0.3 g/kg·body mass of SB on three occasions (SB1, SB2, and SB3) and 0.3 g/kg·body mass of placebo on a further occasion. Blood bicarbonate was determined before and every 10 min following supplement ingestion for 3 hr and then every 20 min for a further 1 hr. Side effects were reported using an adapted questionnaire at identical time points. Maximal increases in blood bicarbonate with SB were +20.0, +15.2, and +12.6 mM, resulting in maximal bicarbonate concentrations of 42.8, 39.3, and 36.2 mM. Area under the curve was SB1: 8,328 mM/min; SB2: 7,747 mM/min; SB3: 7,627 mM/min, and 6,436 mM/min for placebo. Side effects with SB were scarce. Maximal bicarbonate increases were well above those shown previously, with minimal side effects, indicative of minimal neutralization of bicarbonate in the stomach. The large increases in circulating bicarbonate and minimal side effects experienced by our postgastric surgery bypass patient are indicative that minimizing neutralization of bicarbonate in the stomach, as would occur with enteric coated capsules, may optimize SB supplementation and thus warrants investigation.

Is Transcellular Potassium Shifting With Insulin, Albuterol, or Sodium Bicarbonate in Emergency Department Patients With Hyperkalemia Associated With Recurrent Hyperkalemia After Dialysis?

BACKGROUND: Emergency department (ED) treatment of hyperkalemia often involves shifting potassium into the intracellular space. There is uncertainty whether transcellular shifting causes insufficient potassium removal during hemodialysis, resulting in a subsequent need for further medical therapy or multiple sessions of hemodialysis. OBJECTIVE: We sought to determine whether transcellular potassium shifting in ED patients with hyperkalemia who undergo hemodialysis is associated with recurrent hyperkalemia with or without repeat hemodialysis within 24 h. METHODS: This was a retrospective observational study of ED patients with a potassium value > 5.3 mmol/L and ≥1 hemodialysis run. Transcellular shifting medications were defined as albuterol, insulin, and sodium bicarbonate. Primary outcomes were recurrent hyperkalemia with and without repeat hemodialysis within 24 h of the initial dialysis run. Generalized estimating equation models were created for the outcomes using administration of a shifting medication as the primary predictor. RESULTS: Four hundred seventy-nine encounters were identified. In 238 (50%) encounters, a shifting medication was administered. There were 85 outcomes of recurrent hyperkalemia and 36 outcomes of recurrent hyperkalemia with repeat hemodialysis. After adjustment, administration of shifting medications was not associated with recurrent hyperkalemia (adjusted odds ratio 1.26, 95% confidence interval 0.71-2.23) or recurrent hyperkalemia with repeat dialysis (adjusted odds ratio 1.90, 95% confidence interval 0.80-4.48). CONCLUSIONS: Administration of transcellular shifting medications for hyperkalemia in the ED was not associated with either recurrent hyperkalemia after hemodialysis or the need for a second dialysis session within 24 h. Our findings address the uncertainty regarding transcellular potassium shifting before emergent dialysis and support safe ED administration of medications that shift potassium to the intracellular space.

Ayudas ergogénicas en el deporte / Ergogenic aids in sport

Introducción: muy pocos suplementos nutricionales han demostrado científicamente su eficacia como ayuda ergogénica. Esta revisión analizará el monohidrato de creatina (MC), el β-hidroxi-β-metilbutirato (HMB), el bicarbonato sódico (BS), la β-alanina y la cafeína. Objetivos: analizar la eficacia, mecanismos de acción, dosis, efectos adversos y algunos deportes que se pueden beneficiar de su consumo. Métodos: búsqueda en la base de datos PubMed de revisiones bibliográficas de los últimos 15 años y artículos originales de los últimos 5 años de las sustancias estudiadas. Resultados: dosis de MC de 20 g/día durante 4-7 días son eficaces para mejorar la fuerza y la potencia muscular y el rendimiento en sprints cortos y repetidos. El HMB en dosis de 3 g/día durante un mínimo de 2 semanas contribuye al aumento de la masa magra y de la masa libre de grasa. La ingesta de 0,3 g/kg de BS mejora el rendimiento en pruebas de 400-1.500 m de atletismo y en sprints intermitentes. Por su parte, dosis de 80 mg/kg/día de β-alanina durante 4-10 semanas pueden mejorar el rendimiento en ejercicios intermitentes de alta intensidad. Finalmente, la cafeína en dosis de 2 mg/kg mejora la capacidad de reacción y en dosis de 3-6 mg/kg mejora el rendimiento en pruebas de resistencia aeróbica. Conclusiones: los suplementos revisados presentan una demostrada eficacia en el rendimiento físico, pero hay que tener en cuenta que la mayoría de los estudios se han realizado con deportistas de nivel recreativo. Generalmente, la mejora del rendimiento físico con estos suplementos es menor cuanto mejor es el nivel deportivo del individuo; sin embargo, un incremento de apenas un 1% permite a veces avanzar varios puestos en una final. Finalmente, se debe llamar la atención sobre la importancia de optimizar la alimentación antes de plantearse la introducción de suplementos deportivos, especialmente en niños y jóvenes. Las sustancias que hemos analizado poseen una base científica que respalda su efecto ergogénico. Todas ellas se pueden encontrar en el mercado con Certificado de Calidad y Pureza (AU)

Introduction: Very few nutritional supplements have scientifically demonstrated their effectiveness as an ergogenic aid. This review will examine creatine monohydrate (MC), the β-hydroxy-β-methylbutyrate (HMB), sodium bicarbonate (BS), the β-alanine and caffeine. Objectives: To analyze the efficacy, mechanisms of action, dose, side effects and some sports that can benefit from their consumption. Methods: Searching in PubMed bibliographic database reviews from the last 15 years and original articles from the last 5 years of the studied substances. Results: Doses of 20 mg/day for 4-7 days are effective in improving strength and muscular power and performance in short and repeated sprints. HMB at doses of 3 g/day for at least 2 weeks contributes to increased lean mass and fat-free mass. The intake of 0.3 g/kg of BS improves performance on tests of 400-1,500 meters in athletics and intermittent sprints. Meanwhile, doses of 80 mg/kg/day of β-alanine for 4-10 weeks may improve performance in high-intensity intermittent exercise. Finally, caffeine at doses of 2 mg/kg improves responsiveness and 3-6 mg/kg improves performance in endurance tests. Conclusions: The revised supplements have shown their efficacy in physical performance, but it is needed to keep in mind that most studies have been conducted with recreational-level athletes. Generally, the better the individual´s fitness level is the less improvement in physical performance the supplement shows. However, an increase of only 1% may sometimes allow the athlete to advance several positions in a final. Finally, we should draw attention to the importance of optimizing nutrition before considering the introduction of sports supplements, especially in children and youth. All analyzed substances have scientific basis supporting its ergogenic effect. All of them can be found in the market with Certificate of Quality and Purity (AU)

Effect of Sodium Bicarbonate Buccal Infiltration on the Success of Inferior Alveolar Nerve Block in Mandibular First Molars with Symptomatic Irreversible Pulpitis: A Prospective, Randomized Double-blind Study.

INTRODUCTION: The purpose of this prospective, randomized, double-blind study was to evaluate the effect of a buccal infiltration of sodium bicarbonate on the anesthetic success of the inferior alveolar nerve block (IANB) for mandibular first molars in patients with symptomatic irreversible pulpitis. METHODS: One hundred patients diagnosed with symptomatic irreversible pulpitis of a mandibular first molar were selected. The patients randomly received a buccal infiltration injection of either 0.7 mL 8.4% sodium bicarbonate with 0.3 mL 2% lidocaine containing 1:80,000 epinephrine or 0.7 mL sterile distilled water with 0.3 mL 2% lidocaine containing 1:80,000 epinephrine in a double-blind manner. After 15 minutes, all the patients received conventional IANB injection using 3.6 mL 2% lidocaine with 1:80,000 epinephrine. Access cavity preparation was initiated 15 minutes after the IANB injection. Lip numbness was a requisite for all the patients. Success was determined as no or mild pain on the basis of Heft-Parker visual analog scale recordings upon access cavity preparation or initial instrumentation. Data were analyzed using the t, chi-square and Mann-Whitney U tests. RESULTS: The success rate after the buccal infiltration of sodium bicarbonate was 78%, whereas without the buccal infiltration of sodium bicarbonate it was 44% (P < .001). CONCLUSIONS: A buccal infiltration of 0.7 mL 8.4% sodium bicarbonate increased the success rate of IANBs in mandibular first molars with symptomatic irreversible pulpitis.

Investigation and Evaluation of an in Situ Interpolymer Complex of Carbopol with Polyvinylpyrrolidone as a Matrix for Gastroretentive Tablets of Ranitidine Hydrochloride.

Carbopol (CP) is a biocompatible bioadhesive polymer used as a matrix for gastroretentive (GR) tablets, however, its rapid hydration shortens its bioadhesion and floating when incorporated in effervescent formulae. The interpolymer complexation of CP with polyvinylpyrrolidone (PVP) significantly reduced the excessive hydration of CP, prolonging floating and maintaining the mucoadhesiveness. In early attempts, a lengthy process was followed to prepare such an interpolymer complex. In this study, an in situ interpolymer complexation between CP and two grades of PVP (K25 and K90) in 0.1 N HCl was investigated and characterized by Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Hence, directly compressed GR tablets of different combinations of PVP and CP with sodium bicarbonate (SB) as an effervescent agent were examined for prolonged gastroretention and sustained release of ranitidine hydrochloride (RHCl) as a model drug. Tablets were evaluated for in vitro buoyancy, bioadhesiveness, swelling, and drug release in 0.1 N HCl. All GR tablets containing PVP-CP combinations achieved more prolonged floating (>24 h) than CP tablets (5.2 h). Their bioadhesiveness, swelling, and drug release were dependent on the PVP molecular weight and its ratio to CP. Drug release profiles of all formulae followed non-Fickian diffusion. Formula containing the PVP K90-CP combination at a respective ratio of 1 : 3 (P90C13) was a promising system, exhibiting good floating and bioadhesive properties as well as sustained drug release. Abdominal X-ray imaging of P90C13 formula, loaded with barium sulfate, in six healthy volunteers showed a mean gastric retention period of 6.8±0.3 h.

Efecto agudo del baño con citrato sobre la alcalemia postdiálisis / Acute effect of citrate baths on post-dialysis alkalemia

INTRODUCCIÓN: La corrección de la acidosis metabólica provocada por la insuficiencia renal se consigue aportando bicarbonato durante la diálisis. Para evitar la precipitación de carbonato cálcico y magnésico que se produce en el líquido de diálisis (LD) al añadir bicarbonato, es necesario añadir un ácido, habitualmente acetato, que no está exento de efectos secundarios. Así, el citrato se presenta como una alternativa ventajosa al acetato, aunque sus efectos agudos no se conocen con precisión. OBJETIVO: Evaluar el efecto agudo sobre los parámetros del equilibrio ácido base y del metabolismo calcio-fósforo con la utilización de un líquido de diálisis con citrato en lugar de acetato. MATERIAL Y MÉTODOS: Estudio prospectivo y cruzado realizado en veinticuatro pacientes (15 hombres y 9 mujeres). Todos los pacientes se dializaron con monitor AK- 200-Ultra-S con líquido de diálisis SoftPac®, elaborado con 3 mmol/l de acetato y con SelectBag Citrate®, con 1 mmol/l de citrato, libre de acetato. Se extrajeron pre y post-diálisis: gasometría venosa, calcio (Ca), calcio iónico (Cai), fósforo (P) y hormona paratiroidea (PTH). RESULTADOS: Encontramos diferencias (p < 0,05) cuando utilizamos el baño con citrato (C) frente a acetato (A) en los valores postdiálisis de: pH (C: 7,43 (0,04) vs. A: 7,47 (0,05)), bicarbonato (C: 24,7 (2,7) vs. A: 27,3 (2,1) mmol/L), exceso de base (BEecf) (C: 0,4 (3,1) vs A: 3,7 (2,4) mmol/L), calcio corregido (Cac) (C: 9,8 (0,8) vs A: 10,1 (0,7) mg/dl) y Cai (C: 1,16 (0,05) vs A: 1,27 (0,06) mmol/L). No encontramos diferencias en ninguno de los parámetros medidos prediálisis. CONCLUSIÓN: La diálisis con citrato consigue un mejor control de equilibrio ácido base postdiálisis disminuyendo/evitando la alcalemia postdiálisis y un menor aumento de calcio corregido (Cac) y Cai. Este hallazgo es de especial interés en pacientes con factores predisponentes a arritmias, pacientes con insuficiencia respiratoria, retención de carbónico, calcificaciones y hepatopatía avanzada

Introduction: Correcting metabolic acidosis provoked by renal failure is achieved by supplying bicarbonate during dialysis. To prevent the precipitation of calcium and magnesium carbonate produced in the dialysis fluid (DF) when bicarbonate is added, it is necessary to add an acid(normally acetate), which involves secondary effects. Consequently, citrate is presented as an advantageous alternative to acetate, although its acute effects are not known with precision. Objective: Our objective was to assess the acute effect of using a DF with citrate instead of acetate on the parameters of acid-base balance and of phosphorus-calcium metabolism. Material and methods: We carried out a prospective, cross-over study on 24 patients (15 males and 9 females). All the patients were dialysed using an AK 200 ULTRA-S monitor with SoftPacRDF, prepared with 3 mmol/l of acetate, and with SelectBag CitrateR, with 1 mmol/l of acetate freecitrate. Before and after dialysis we extracted: venous blood gases, calcium (Ca), ionized calcium (Cai), phosphorus (P) and parathyroid hormone (PTH).Results: We found differences (P<.05) when we used a dialysate with citrate (C) compared with using acetate (A) in the post-dialysis values of pH (C: 7.43 [0.04] vs A: 7.47 [0.05]), bicarbonate(C: 24.7 [2.7] vs A: 27.3 [2.1] mmol/L), base excess of extracellular fluid (BEecf) (C: 0.4 [3.1] vs A: 3.7[2.4] mmol/L), corrected calcium (cCa) (C: 9.8 [0.8] vs A: 10.1 [0.7] mg/dl) and Cai (C: 1.16 [0.05] vsA: 1.27 [0.06] mmol/L). We found no differences in any of the parameters measured before dialysis. Conclusion: Dialysis with citrate achieves better post-dialysis acid-base balance, lowering/avoiding post-dialysis alkalemia and producing a lower increase in corrected calcium (Cac) and Cai. This finding is of special interest for patients with predisposing factors to arrhythmia and patients with respiratory failure, carbon dioxide retention, calcifications or advanced hepatopathy (AU)

Multi-compound polarization by DNP allows simultaneous assessment of multiple enzymatic activities in vivo.

Methods for the simultaneous polarization of multiple 13C-enriched metabolites were developed to probe several enzymatic pathways and other physiologic properties in vivo, using a single intravenous bolus. A new method for polarization of 13C sodium bicarbonate suitable for use in patients was developed, and the co-polarization of 13C sodium bicarbonate and [1-(13)C] pyruvate in the same sample was achieved, resulting in high solution-state polarizations (15.7% and 17.6%, respectively) and long spin-lattice relaxation times (T1) (46.7 s and 47.7 s respectively at 3 T). Consistent with chemical shift anisotropy dominating the T1 relaxation of carbonyls, T1 values for 13C bicarbonate and [1-(13)C] pyruvate were even longer at 3 T (49.7s and 67.3s, respectively). Co-polarized 13C bicarbonate and [1-(13)C] pyruvate were injected into normal mice and a murine prostate tumor model at 3T. Rapid equilibration of injected hyperpolarized 13C sodium bicarbonate with 13C CO2 allowed calculation of pH on a voxel by voxel basis, and simultaneous assessment of pyruvate metabolism with cellular uptake and conversion of [1-(13)C] pyruvate to its metabolic products. Initial studies in a Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model demonstrated higher levels of hyperpolarized lactate and lower pH within tumor, relative to surrounding benign tissues and to the abdominal viscera of normal controls. There was no significant difference observed in the tumor lactate/pyruvate ratio obtained after the injection of co-polarized 13C bicarbonate and [1-(13)C] pyruvate or polarized [1-(13)C] pyruvate alone. The technique was extended to polarize four 13C labelled substrates potentially providing information on pH, metabolism, necrosis and perfusion, namely [1-(13)C]pyruvic acid, 13C sodium bicarbonate, [1,4-(13)C]fumaric acid, and 13C urea with high levels of solution polarization (17.5%, 10.3%, 15.6% and 11.6%, respectively) and spin-lattice relaxation values similar to those recorded for the individual metabolites. These studies demonstrated the feasibility of simultaneously measuring in vivo pH and tumor metabolism using nontoxic, endogenous species, and the potential to extend the multi-polarization approach to include up to four hyperpolarized probes providing multiple metabolic and physiologic measures in a single MR acquisition.

Effects of various sodium bicarbonate loading protocols on the time-dependent extracellular buffering profile.

Although much research has investigated the types of exercise that are enhanced with sodium bicarbonate (NaHCO3) ingestion, to date, there has been limited research on the dosage and timing of ingestion that optimizes the associated ergogenic effects. This study investigated the effects of various NaHCO3 loading protocols on the time-dependent blood-buffering profile. Eight male volunteers (age, 22.4 +/- 5.7 yr; height, 179.8 +/- 9.6 cm, body mass, 76.3 +/- 14.1 kg) completed Part A, measures of alkalosis throughout 120 minutes after ingestion of various single NaHCO3 dosages (0.3 gxkg-1, 0.2 gxkg-1, 0.1 gxkg-1, and placebo); and Part B, similar profiles after alternative NaHCO3 loading protocols (single morning dosage [SMD], single evening dosage [SED], and dosages ingested on 3 consecutive evenings [CED]). Results from Part A are as follows. Blood buffering in the 0.1 gxkg-1 condition was significantly lower than the 0.2 g.kg-1 and 0.3 gxkg-1 conditions (p < 0.002), but there was no significant differences between the 0.2 gxkg -1and 0.3 g.kg-1 conditions (p = 0.34). Although the blood buffering was relatively constant in the 0.1 and 0.2 conditions, it was significantly higher at 60 minutes than at 100 minutes and 120 minutes in the 0.3 gxkg-1 condition (p < 0.05). Results from Part B are as follows. Blood buffering for SMD was significantly higher than for SED and CED (p < 0.05). Blood buffering in the SMD condition was significantly lower at 17:00 hours than at 11:00 hours (p = 0.007). The single 0.2 and 0.3 gxkg-1 NaHCO3 dosages appeared to be the most effective for increasing blood-buffering capacity. The 0.2 gxkg-1 dosage is best ingested 40 to 50 minutes before exercise and the 0.3 gxkg-1 dosage 60 minutes before exercise.

Effect of stearic acid on the properties of metronidazole/methocel K4M floating matrices / Efeito do ácido esteárico nas propriedades de metronidazol / Methocel K4M matrizes flutuante

The properties of metronidazole/Methocel K4M sustained release floating tablets have been studied varying the proportion of the lubricant, stearic acid, on formulations with and without sodium bicarbonate. The variables studied include technological properties of the tablets such as tablet hardness and ejection pressure, the drug release profile, the hydration kinetics and the floating behaviour. The presence of stearic acid and sodium bicarbonate improves the floating behaviour for more than 8 hours. The hydration volume, the tablet hardness and the ejection pressure decrease as the stearic acid content increases and the polymer content decreases. Drug dissolution increases with increasing proportions of stearic acid and decreasing proportions of the polymer in the tablets. The presence of sodium bicarbonate extends the differences in dissolution produced by stearic acid. These results are attributed to decreasing matrices coherence with an increasing quantity of stearic acid and a reducing polymer proportion. The carbon dioxide bubbles produced by sodium bicarbonate expand the matrices facilitating the dissolution, although their presence obstructs also the diffusion path through the hydrated gel layer.

Estudaram-se as propriedades de comprimidos flutuantes de metronidazol/Methocel K4M de liberação controlada, variando-se a proporção do lubrificante, ácido esteárico, nas formulações com e sem bicarbonato de sódio. As variáveis estudadas incluem propriedades tecnológicas dos comprimidos, tais como dureza, pressão de ejeção, perfil de liberação do fármaco, cinética de hidratação e comportamento de flutuação. A presença de ácido esteárico e do bicarbonato de sódio melhora o comportamento de flutuação para mais de 8 horas. O volume de hidratação, a dureza e a pressão de ejeção do comprimido decrescem à medida que o conteúdo de ácido esteárico e de polímero diminui. A dissolução do fármaco aumenta com o aumento das proporções de ácido esteárico e a diminuição das proporções de polímero nos comprimidos. A presença de bicarbonato de sódio amplia as diferenças na dissolução produzidas pelo ácido esteárico. Estes resultados são atribuídos à coesão decrescente das matrizes, com o aumento da quantidade de ácido esteárico e a redução da proporção de polímero. Bolhas de dióxido de carbono produzidas pelo bicarbonato de sódio expandem as matrizes, facilitando a dissolução, embora a presença delas obstrua, também, a difusão através da camada de gel hidratado.

Optimización de la actividad de las enzimas pancreáticos con comprimidos entéricos de bicarbonato sódico / Optimization of the bioactivity of pancreatic enzymes with the administration of enteric tablets of sodium bicarbonate

Fundamento. Valorar la efectividad y tolerancia de la administraciónde comprimidos entéricos de bicarbonato sódico con cubiertade ácido resistente con el fin de aumentar el pH duodenal y optimizarla actividad de los enzimas pancreáticos.Método. Fueron incluidos 21 pacientes (66 % varones y 34 % mujeres),con una media de edad de 11 años (intervalo 13-23) y un pesomedio de 32,24 ± 12,2 Kg (intervalo 13-52). Se formularon comprimidosentéricos de bicarbonato sódico de 225 mg con un diámetrode 7 mm con una disgregación de la envoltura a pH 5. Fueron determinadosen estado basal con solo enzimas (B) y tras 15 días detratamiento con bicarbonato (15 g/m2/24 h) repartido con los enzimasa las dosis habituales (CB) los siguientes parámetros en heces:amilasa, lipasa, quimotripsina, grasa, azúcar y proteínas. La dietafue similar durante todo el estudio.Resultados. Las dosis de lipasa administrada a nuestros pacientesmostró una media de 2.812 U (F.I.P)/kg/24 h (rango 5.700 U- 450 U),lo cual conlleva una media de esteatorrea de 7,79 g% (DE 3,28 g%).El estudio estadístico de correlación linear entre el aporte de lipasay los niveles de esteatorrea presentó una correlación negativa (r =0.16). Los resultados en heces mostraron: amilasa u/l (B) 5.273 ±3.825 vs 4.779 ± 3.147 (CB), lipasa u/l 268 ± 189 (B) vs 224 ± 167 (CB);quimotripsina u/l 32 ± 33 (B) vs 31 ± 28 (CB), grasa g% 7,3 ± 3 (B) vs7,79 ± 3,28 (CB), nitrógeno g % 1,6 ± 0,26 (B) vs 1,7 ± 0,32 (CB) y azúcarg% 1,71 ± 0,61 (B) vs 1,9 ± 0,64 (CB).Conclusiones. La determinación de amilasa, lipasa, quimotripsina ygrasa en heces mostraron un ligero descenso en algunos pacientes,pero sin alcanzar diferencia significativa como grupo. Futuros estudioscon un aumento de la dosis de bicarbonato y disgregación dela envoltura a un pH < 5 deberán ser efectuados(AU)

Objective. To evaluate the efficacy and tolerability of the administrationof acid-resistant enteric tablets of sodium bicarbonate toincrease the duodenal pH and optimize the activity of pancreaticenzymes in patients with cystic fibrosis (CF).Method. Twenty-one children (66% male) with CF were includedin the study. Median age was 11 years (range, 13-23), and meanweight was 32.24 ± 12.2 Kg (range, 13-52). Seven-mm sodium bicarbonatetablets (225 mg) were formulated with a coat dissolutionpoint of ph of 5. Stool content of amylase, lipase, chemotrypsine,fat, sugar and proteins were measured at baseline followingadministration of enzymes, and after 15 days of concomitant treatmentwith sodium bicarbonate (15 g/m2/24 hours). The diet wassimilar throughout the study period.Results. The median dose of lipase was 2,812 U (F.I.P.)/kg/24 hours(range 5,700 U-450 U) with a resulting steatorrhea of 7.79 g% (±3.28 g%). There was a negative linear correlation between lipaseadministration and steatorrhea levels (r=0.16). The stool studiesbefore (B) and after concomitant administration of sodium bicarbonate(CB) showed the following: amylase (u/l) 5,273 ± 3,825 (B)vs. 4,779 ± 3,147 (CB); lipase (u/l) 268 ± 189 (B) vs. 224 ± 167 (CB);chemotrypsine (u/l) 32 ± 33 (B) vs. 31 ± 28 (CB); fat (g%) 7.3 ± 3 (B)vs. 7.79 ± 3.28 (CB); nitrogen (g%) 1.6 ± 0.26 (B) vs. 1.7 ± 0.32 (CB);and sugar (g%) 1.71 ± 0.61 (B) vs. 1.9 ± 0.64 (CB).Conclusions. The stool content of amylase, lipase, chemotrypsineand fat showed a mild decrease in some patients after the concomitantadministration of sodium bicarbonate; however, differenceswere not statistically significant. Future studies with higher dosesof sodium bicarbonate and with coat dissolution point at pH < 5should be explored(AU)

Efficacy of oral rehydration therapy solutions containing sodium bicarbonate or sodium acetate for treatment of calves with naturally acquired diarrhea, moderate dehydration, and strong ion acidosis.

OBJECTIVE: To determine and compare the effects of 4 oral replacement therapy (ORT) solutions on acid-base balance, abomasal emptying rate, and plasma volume expansion in calves with naturally acquired diarrhea and moderate dehydration. DESIGN: Prospective study. ANIMALS: 20 calves. PROCEDURES: 20 calves up to 45 days of age were randomly allocated (n = 5/group) to receive 2 L of 1 of 4 treatments via oroesophageal intubation: sodium bicarbonate (150 mmol/L or 300 mmol/L) or sodium acetate (150 mmol/L or 300 mmol/L). The 4 test solutions contained acetaminophen (50 mg/kg [22.7 mg/lb]) and 50 g of glucose monohydrate. Jugular venous blood samples were obtained periodically before and after administration of the ORT solution. Abomasal emptying rate was determined by use of the time to maximal plasma acetaminophen concentration. RESULTS: Plasma bicarbonate concentration increased more rapidly in calves administered bicarbonate-containing ORT solutions, whereas the rate of systemic alkalinization, as assessed via blood pH, did not differ consistently among treatments. The 300 mmol/L ORT solutions were emptied at a significantly slower rate from the abomasum than 150 mmol/L ORT solutions, with no difference in emptying rate between acetate and bicarbonate-containing ORT solutions of similar molality. The 300 mmol/L sodium acetate ORT solution significantly increased plasma volume. CONCLUSIONS AND CLINICAL RELEVANCE: Clinically important differences in the resuscitative response to 300 mmol/L or 150 mmol/L ORT solutions of sodium acetate or sodium bicarbonate were not identified.

Bicarbonate kinetics and predicted energy expenditure in critically ill children.

BACKGROUND: To determine nutrient requirements by the carbon oxidation techniques, it is necessary to know the fraction of carbon dioxide produced during the oxidative process but not excreted. This fraction has not been described in critically ill children. By measuring the dilution of (13)C infused by metabolically produced carbon dioxide, the rates of carbon dioxide appearance can be estimated. Energy expenditure can be determined by bicarbonate dilution kinetics if the energy equivalents of carbon dioxide (food quotient) from the diet ingested are known. OBJECTIVE: We conducted a 6-h, primed, continuous tracer infusion of NaH(13)CO(3) in critically ill children fed parenterally or enterally or receiving only glucose and electrolytes, to determine bicarbonate fractional recovery, bicarbonate rates of appearance, and energy expenditure. DESIGN: Thirty-one critically ill children aged 1 mo-20 y who were admitted to a pediatric intensive care unit at a tertiary-care center were studied. Patients were stratified by age, BMI, and severity score (PRISM III). RESULTS: Fractional bicarbonate recovery was 0.69, 0.70, and 0.63, respectively, for the parenterally fed, enterally fed, and glucose-electrolytes groups, and it correlated with the severity of disease in the parenteral (P < 0.01) and glucose-electrolytes (P < 0.05) groups. Rates of appearance varied between 0.17 and 0.19 micromol . kg(-1) . h(-1) With these data and estimates of the energy equivalents of carbon dioxide (a surrogate for respiratory quotient), energy expenditure was determined. CONCLUSIONS: The 2001 World Health Organization and Schofield predictive equations overestimated and underestimated, respectively, energy requirements compared with those obtained by bicarbonate dilution kinetics. Bicarbonate kinetics allows accurate determination of energy needs in critically ill children.

Relative bioavailability of new formulation of paracetamol effervescent powder containing sodium bicarbonate versus paracetamol tablets: a comparative pharmacokinetic study in fed subjects.

OBJECTIVE: the aim of this relative bioavailability study was to determine the rate and extent of absorption of Alikal Dolor (effervescent powder containing paracetamol 500 mg/sodium bicarbonate 2318 mg)--test formulation (T) in relation to Parageniol (paracetamol 500 mg coated tablets)--reference formulation (R). METHODS: 18 healthy volunteers (10 male and 8 female aged between 21 and 46 years) received, after 2 h of standardized breakfast, a single oral dose with 220 ml of water, in an open, randomized, crossover study, with a 7-day wash-out period. Paracetamol concentrations were established at 0, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 75, 90 min and at 2, 4, 6, 8 and 10 h postdose by HPLC with an ultraviolet detector. RESULTS: the regression coefficient determined for paracetamol calibration curves was 0.9983 +/- 0.0034 and the working range was from 0.2 to 50 microg/ml. The quantification limit was 0.2 microg/ml. The rate of absorption was significantly greater (p < 0.03) for T (T(max) = 20.4 min) compared with R (T(max) = 38.4 min). Extent of absorption over the first 30 min postdose AUC((0-30 min)) was 4.21-fold greater (p < 0.03) for T compared with R, without differences between C(max.) The 90% CI on the geometric mean for C(max), AUC((0-10 h)) and AUC((0-)) ratios (T/R) were within the limits of 0.80-1.25, indicating both formulations were bioequivalent with respect to these parameters. CONCLUSION: paracetamol was absorbed at least twice as fast from T-containing sodium bicarbonate compared with R. This pharmacokinetic feature could prove crucial from the therapeutic point of view as it would allow a lower latency in the action time of paracetamol in producing its analgesic and antithermal effect.