Preformulation of a liquid dosage formulation of captopril for pediatric use: drug-excipient compatibility and stability studies

Currently, medications used in children are typically modified from pharmaceutical dosage forms designed for adults. Captopril is widely adapted to liquid formulations for use in hospitals. Its stability in the aqueous medium is reduced since it undergoes oxidation producing captopril disulfide (its main metabolite). The aim of this formulation study was to suggest favorable conditions for the development of a stable captopril formulation. The compatibility between the drug and excipients was evaluated by differential scanning calorimetry analysis (DSC). For studies in solution, different formulations were prepared according to a factorial design varying EDTA concentration, water purity and pH. The resultant formulations were stored at 60°C and analyzed over a twelve-day period using HPLC. The DSC curves obtained suggested, although not conclusive to elucidation, interactions of captopril with citric acid and sucralose. The stability study of these solutions revealed that the variables significantly influenced captopril content, which degraded at zero order kinetics and rates differing by a factor of up to 7 times, where pH proved the most influential factor. Interactions between variables were observed. Therefore, development of a stable captopril formulation is feasible provided EDTA and a buffering agent is used at suitable concentrations (0.08% and pH 3.85).

Volume de dipirona para via oral versus tipo de conta-gotas, temperatura e ângulos de gotejamento / The volume of dipyrone for oral use versus dropper type, temperature and drip angles / Volumen de dipirona (metamizol) para vía oral versus tipo cuentagotas, temperatura y ángulo de goteo

Objetivo: determinar as diferenças entre volume e número de gotas de dipirona (via oral) por mililitro controlando algumas variáveis. Método: trata-se de um estudo experimental, com abordagem quantitativa, que foi realizado a partir de dados obtidos em experimentos realizados em laboratório, com dois tipos de conta-gotas, temperaturas de 5o e 35o Celsius, além da temperatura ambiente (30o Celsius), de laboratório e os ângulos de 90°, 60° e 45° utilizados para dispensar dipirona. Resultados: com base nos dados coletados, considerou-se que o ângulo de maior confiança para atingir o volume de 20 gotas por cada ml é o ângulo de 90o com o conta-gotas de vidro; em relação à temperatura, a maior confiança no volume de gotas desejado foi alcançada no intervalo de 5o e 30oCelsius. Conclusão: os resultados indicam a necessidade de seguir rigorosamente as orientações do fabricante para que se possa atingir a dose certa na administração de medicamento.

Objective: to determine the differences between volume and number of drops of dipyrone (oral) per milliliter, while controlling some variables. Method: this study applied quantitative analysis to data obtained in laboratory experiments with two types of droppers, temperatures of 5o and 35o Celsius, in addition to ambient temperature (30o Celsius), and the 90°, 60° and 45° angles used to dispense dipyrone. Results: based on the data collected, it was considered that, with the glass dropper, the angle of greatest confidence to achieve the volume of 20 drops per ml is 90o. In relation to temperature, the highest confidence in the desired volume of drops was achieved in the 5o to 30o Celsius interval. Conclusion: the results indicate the need to follow manufacturer's guidelines strictly, so as to achieve the correct dose for drug administration.

Objetivo: determinar las diferencias entre volumen y número de gotas de dipirona (vía oral) por mililitro controlando algunas variables. Método: se trata de un estudio experimental, con enfoque cuantitativo realizado con datos obtenidos en experimentos realizados en laboratorio, con dos tipos de cuentagotas, temperaturas de 5o y 35o Celsius, temperatura ambiente (30° Celsius) de laboratorio y los ángulos de 90°, 60° y 45° para gotear dipirona. Resultados: con base en los datos recolectados, se consideró que el ángulo de mayor confianza para alcanzar el volumen de 20 gotas por cada ml es el ángulo de 90o con el cuentagotas de vidrio. Respecto a la temperatura, la mayor confianza en el volumen de gotas deseado fue alcanzada en el intervalo de 5o y 30o Celsius. Conclusión: los resultados indican la necesidad de seguir rigurosamente las orientaciones del fabricante para alcanzar la dosis correcta en la administración de medicamentos.

Comparison of effect and safety of different dosages of alteplase in the treatment of elderly patients with acute cerebral infarction / 中国基层医药

Objective To compare the effect of different dosages of alteplase in the treatment of elderly patients with acute cerebral infarction,as well to evaluate the safety.Methods From January 2016 to June 2017,82 patients with acute cerebral infarction in the Hospital of Changping District were chosen in this study.The patients were randomly divided into 2 groups according to the digital table:41 patients in study group (0.6 mg/kg alteplase) and 41 patients in control group (0.9mg/kg alteplase).The effective rate and incidence of hemorrhage were compared between the two groups.Results The effective rate of the study group was 95.13％ (39/41),which of the control group was 100.00％ (41/41),the difference was not statistically significant (Z =4.982,P ＞ 0.05).The incidence rate of hemorrhage in the study group was 7.32％ (3/41),which in the control group was 24.39％ (10/41),the difference was statistically significant (x2 =6.248,P ＜ 0.05).Conclusion The effect of different dosages of alteplase demonstrates no significant difference in the treatment of elderly patients,and the safety of low dose is more reliable.

Efficacy and safety of tacrolimus for patients with refractory IgA nephropathy / 第二军医大学学报

Objective To evaluate the efficacy and safety of tacrolimus (TAC) therapy in patients with refractory IgA nephropathy. Methods Nine IgA nephropathy patients were included in this study were treated from Jun. 2008 tc Sep. 2013 in Changzheng Hospital of Second Military Medical University. All patients received TAC therapy after the renin-angiotensin system (RAS) blockade therapy and steroid therapy failed. The main outcome was complete or partial remission. Secondary outcomes included the time required to remission, the frequency of recurrence, TAC dosage and adverse events. Results The initial dosage of TAC" was (1. 89 + 0. 33) mg/d. After treatment with TAC for 6 months, 6 patients achieved complete remission, 2 partial remission and 1 treatment resistance, and most of the remission patients achieved remission during the first 2 months of TAC therapy. The urine protein level of enrolled patients was significantly decreased ([3. 05 ± 1. 35] g/24 h vs [0. 85±1. 54] g/24 h. P<0. 05) and the serum album level of all patients was significantly improved ([27. 00±8. 37] g/L vs [37. 33±8. 08] g/L. P<0. 05). One patient receiving TAC" therapy presented worsened hypertension, and no other adverse event was observed in this study. Three of 8 proteinuria remission patients had relapses find achieved remission by adjusting the dosages of steroids and tacrolimus. Conclusion TAC ear improve proteinuria in patients with refractory IgA nephropathy, with less adverse reactions.

Serum levels of vancomycin: is there a prediction using doses in mg/kg/day or m2/day for neonates?

Abstract Coagulase-negative Staphylococcus has been identified as the main nosocomial agent of neonatal late-onset sepsis. However, based on the pharmacokinetics and erratic distribution of vancomycin, recommended empirical dose is not ideal, due to the inappropriate serum levels that have been measured in neonates. The aim of this study was to evaluate serum levels of vancomycin used in newborns and compare the prediction of adequate serum levels based on doses calculated according to mg/kg/day and m2/day. This is an observational reprospective cohort at a referral neonatal unit, from 2011 to 2013. Newborns treated with vancomycin for the first episode of late-onset sepsis were included. Total dose in mg/kg/day, dose/m2/day, age, weight, body surface and gestational age were identified as independent variables. For predictive analysis of adequate serum levels, multiple linear regressions were performed. The Receiver Operating Characteristic curve for proper serum vancomycin levels was also obtained. A total of 98 patients received 169 serum dosages of the drug, 41 (24.3%) of the doses had serum levels that were defined as appropriate. Doses prescribed in mg/kg/day and dose/m2/day predicted serum levels in only 9% and 4% of cases, respectively. Statistical significance was observed with higher doses when the serum levels were considered as appropriate (p < 0.001). A dose of 27 mg/kg/day had a sensitivity of 82.9% to achieve correct serum levels of vancomycin. Although vancomycin has erratic serum levels and empirical doses cannot properly predict the target levels, highest doses in mg/kg/day were associated with adequate serum levels.

Prospective validation of a novel dosing scheme for intravenous busulfan in adult patients undergoing hematopoietic stem cell transplantation

The objective of this study was to externally validate a new dosing scheme for busulfan. Thirty-seven adult patients who received busulfan as conditioning therapy for hematopoietic stem cell transplantation (HCT) participated in this prospective study. Patients were randomized to receive intravenous busulfan, either as the conventional dosage (3.2 mg/kg daily) or according to the new dosing scheme based on their actual body weight (ABW) (23×ABW(0.5) mg daily) targeting an area under the concentration-time curve (AUC) of 5924 µM·min. Pharmacokinetic profiles were collected using a limited sampling strategy by randomly selecting 2 time points at 3.5, 5, 6, 7 or 22 hours after starting busulfan administration. Using an established population pharmacokinetic model with NONMEM software, busulfan concentrations at the available blood sampling times were predicted from dosage history and demographic data. The predicted and measured concentrations were compared by a visual predictive check (VPC). Maximum a posteriori Bayesian estimators were estimated to calculate the predicted AUC (AUC(PRED)). The accuracy and precision of the AUC(PRED) values were assessed by calculating the mean prediction error (MPE) and root mean squared prediction error (RMSE), and compared with the target AUC of 5924 µM·min. VPC showed that most data fell within the 95% prediction interval. MPE and RMSE of AUCPRED were -5.8% and 20.6%, respectively, in the conventional dosing group and −2.1% and 14.0%, respectively, in the new dosing scheme group. These fi ndings demonstrated the validity of a new dosing scheme for daily intravenous busulfan used as conditioning therapy for HCT.

A case control study on risk factors for dose wearing off in Parkinson's disease patients / 中华老年心脑血管病杂志

Objective To study the risk factors for dose wearing off (WO)in PD patients .Methods One hundred and thirty-three PD patients were recruited in this study according to the UKPDBB criteria .Their dose WO was diagnosed according to the Wo questionnaire 9 (WOQ-9) .The pa-tients were divided into WOQ-9 (+ ) group (n=111) and WOQ-9 (-) group (n=22) .The pa-tients in WOQ-9 (+) group were further divided int WO (+ ) group (n=59) and WO (-) group (n=52) .The difference in their clinical and therapeutic parameters was compared .Results The dose WO was observed in 83 .5% of the 133 PD patients ,53 .2% of which accorded with the dose WO clinical definition .T he disease onset age ,disease course ,maximal levodopa daily dose and ac-cumulated levodopa dose differed greatly in WOQ-9 (+ ) group and WOQ-9 (-) group (P<005) . The disease course ,H-Y stage ,UPDRS score ,tetany score ,maximal levodopa daily dose ,levodopa dose per body weight and accumulated drug use time differed greatly in WOQ-9 (+ ) group and WOQ-9 (-) group (P< 0 .01) .The major risk of dose WO was the levodopa dose per body weight (OR=1.364 ,P<0 .05) .Conclusion Dose WO is related with the progress of disease and the use of levodopa .Levodopa dose per body weight is an independent risk factor for dose WO .

Effect of esomeprazole with different dosage and usage on intragastric pH of healthy volunteers / 中华消化杂志

Objective To evaluate the effect of csomeprazole with different dosage and usage regimes on intragastric pH of healthy volunteers. Methods It was a randomized, open-label, three-way crossover study. Fifteen healthy volunteers received esomeprazole with 3 different dosages (20 mg or 40 mg once daily or 20 mg twice daily) with 5 days each. Twenty-four continuous ambulatory intragastric pH was recorded at day 5 of each regime. Results The mean time of intragastric pH above 4 was higher in regime of 20 mg twice daily [(21.16 ±2.45) hours ] than that in regimes of 20 mg once daily [(18. 70±4.19) hours] and 40 mg once daily [(19.27±2.68 ) hours] (P<0.05). The percentages of the sleeping and active period that pH remained above 3,4,5 were significantly higher in regime of 20 mg twice daily(day time:95.0%±7.5% ,92.0%±10.6% ,86.7% ± 14.5% ;night time:93.2%± 13.1% ,87.8%±20.3% ,78.6%±28. 9 % )compared with regimes of 40 mg once daily(day time:87.9%±9.5% ,83.5%±11.7%,75.6%±15.50%, night time:75. 7%±20. 8%,66. 9%±23. 8%,53. 3%±30. 3%) and 20 mg once daily(day time: 85.1 % ± 16.3 %, 81.1 %± 18. 1%, 71.5 % ± 20.3 % ; night time: 72.9 % ± 30.5 %,67.2 % ± 31.9 %, 55.7 % ± 31.8 % ) (P< 0.05 ). Esomeprazole maintained intragastric pH above these pH thresholds for a similar propotion of sleeping and active periods with 40 mg once daily and 20 mg once daily.Conclusions Esomeprazole has strong inhibitory effect on intragastric acid. The regime of 20 mg twice daily is superior to 40 mg once daily and 20 mg once daily in both day and night time acid inhibition.There is no difference between esomeprazole 40 mg once daily and 20 mg once daily.