Metabolic study of trimetazidine using ultra-high performance liquid chromatography-tandem mass spectrometry

Abstract In the present study, the application of ultra-high performance liquid chromatography-tandem mass spectrometry allowed us to study of known-as well as hitherto unknown-trimetazidine (TMZ) metabolites in human urine and to propose their renal excretion profiles. Urine samples from a healthy volunteer were analyzed at baseline and at 0-4 h, 4-8 h, 8-12 h, and 12-24 h after a single dose of TMZ. A dilute-and-shoot procedure was used as sample treatment before separation. Full-scan spectra of possible metabolites were acquired. Additionally, product ion scan spectra of precursor ions of interest were also acquired at two collision energies. Intact TMZ was a major excretion product, with a maximum concentration at 4-8 h after administration. Moreover, five minor metabolites were observed, namely trimetazidine-N-oxide (M1), N-formyl trimetazidine (M2), desmethyl-trimetazidine O-sulfate (M3), desmethyl-trimetazidine O-glucuronide (M4), and desmethyl-trimetazidine-N-oxide-O-glucuronide (M5). Metabolite M5 has not previously been reported. Excretion curves were constructed based on the chromatographic peak areas of specific mass transitions (precursor ion > product ion) related to each of the detected metabolites

Development and validation of a simple and noninvasive method for salivary uric acid: potential applications for monitoring the salivary uric acid level in healthy volunteers and gout patients

Abstract Serum uric acid (UA) is a traditional biomarker in the clinical diagnosis of gout and hyperuricemia. However, serum treatment and storage are cumbersome, and wounds are susceptible to infection. Therefore, in this study, a simple and noninvasive method was developed to detect the UA in human saliva to monitor the gout. An Inertsil ODS-3 column was used for the analysis under the condition of isocratic elution with the mixed solution phosphate buffer (74 mM, pH=2.2): Methanol=98:2 (v:v) and the UV detection at 284 nm. Using salivary UA data from healthy volunteers (HVs) (n=68) and gout patients (GPs) (n=14), we examined the salivary UA difference in their content. The intra-and inter-day accuracy and precision (RSD %) were less than 2.56%, the limit of detection (LOD) of UA was 5.0 ng/mL, the mean recoveries of the corresponding compounds were 102.48%. Saliva levels of UA in HVs and GPs were 35.26±14.06 µg/mL and 91.96±23.90 µg/mL, respectively. The concentrations of salivary UA in GPs were significantly higher than those in HVs ( p < 0.001). This method was also expected to monitor the hyperuricemia and other metabolic disorders in the future

¿Es el desplazamiento discal sinónimo de patología articular temporomandibular? Correlación clínico-radiológica y prevalencia de trastornos internos en sujetos voluntarios asintomáticos / Is disc displacement synonymous with temporomandibular joint pathology? Clinical-radiological correlation and prevalence of internal disorders in asymptomatic volunteers subjects

INTRODUCCIÓN: Los trastornos internos (TI) de la articulación temporomandibular (ATM) constituyen la condición clínica articular más frecuente en pacientes con trastornos temporomandibulares (TTM). Presentes hasta en un 80-90 % de los casos sintomáticos, no se sabe por qué, su presencia en sujetos asintomáticos no causa dolor ni disfunción. En contraposición, una posición normal del disco ha sido descrita en un 16-23 % de pacientes sintomáticos. OBJETIVOS: Analizar la prevalencia de TI de la ATM en sujetos voluntarios asintomáticos y qué características clínico-radiológicas podrían favorecer su presencia o desarrollo. MATERIAL Y MÉTODO: Se diseñó un estudio descriptivo, observacional, transversal. Se seleccionaron 43 sujetos de una población de 253 residentes que realizaban su formación médica especializada. El estudio fue desarrollado en varias fases. Fase I: Anamnesis y examen clínico. Empleo del índice craneomandibular de Fricton (ICM); Fase II: Adquisición y evaluación de imágenes de Resonancia Magnética (RMN). Las imágenes fueron procesadas a formato DICOM 4.0 y evaluadas por dos examinadores externos. Fase III: Análisis morfoestructural de las ATM. Las imágenes de RMN fueron analizadas empleando el programa informático Osirix® V 3.5.1. RESULTADOS: Setenta y dos articulaciones (pertenecientes a 36 sujetos) fueron finalmente analizadas. La edad media fue de 28,39 ± 3,70 años con una distribución por sexos de 47,2 % hombres y de 52,8 % mujeres. El análisis inferencial mostró resultados estadísticamente significativos en relación con las variables sexo (p = 0,021), chasquido articular (p = 0,007), valor del ICM (p = 0,000296), morfología discal (p = 1,032 X 10-8), morfología condilar (p = 2,116 X 10-8), posición condilar en el interior de la ATM (longitudes posterior y superior, p = 5,385 X 10-9; p = 0,000245, respectivamente) y morfología de la fosa articular (p = 0,024). CONCLUSIONES: Existe una elevada prevalencia de TI de la ATM en los sujetos asintomáticos analizados. Ciertos criterios clínicos (chasquido articular) y radiológicos (morfología discal alargada/doblada, cóndilo y fosa aplanados y posición más posterior y craneal del cóndilo mandibular) podrían ser considerados como predictores o relacionados con la presencia de desplazamiento discal. El ICM podría constituir una herramienta útil en el diagnóstico de patología articular de la ATM

INTRODUCTION: Internal derangements (IDs) of the temporomandibular joint (TMJ) constitute the most common clinical joint condition in patients with temporomandibular disorders (TMDs). Present in up to 80-90 % of symptomatic cases, it is not known why, its presence in asymptomatic subjects does not cause pain or dysfunction. In contrast, a normal position of the disc has been described in 16-23 % of symptomatic patients. OBJECTIVES: To analyze the prevalence of IDs of the TMJ in asymptomatic voluntary subjects and what clinical-radiological characteristics could favor their presence or development. MATERIAL AND METHODS: A descriptive, observational, cross-sectional study was designed. Fortythree subjects from a population of 253 residents who performed their training program were selected. The study was carried out in several phases. Phase I: Anamnesis and clinical examination. Use of the Fricton Cranio-mandibular Index (CMI); Phase II: Acquisition and evaluation of Magnetic Resonance Imaging (MRI). The images were processed in DICOM 4.0 format and evaluated by two external examiners. Phase III: Morpho-structural analysis of the TMJs. The MRI were analyzed using the Osirix® V 3.5.1 Software. RESULTS: Seventy-two joints (belonging to 36 subjects) were finally analyzed. The mean age was 28.39 ± 3.70 years with a distribution by sex of 47.2% men and 52.8 % women. The inferential analysis showed statistically significant results in relation to the variables sex (p = 0.021), joint click (p = 0.007), CMI value (p = 0.000296), disc morphology (p = 1.032x10-8), condylar morphology (p = 2.116x10-8) and condylar position inside the TMJ ((posterior and superior lengths, p = 5.385x10-9; p = 0.000245, respectively) and morphology of the joint fossa (p = 0.024). CONCLUSIONS: A high prevalence of IDs in asymptomatic subjects is present in our study. Certain clinical (joint clicking) and radiological criteria (an elongated or bent disc morphology, a flattened condyle and fossa and a more posterior and cranial position of the mandibular condyle) could be considered as predictors or be related to the presence of disc displacement. The CMI could be a useful tool in the diagnosis of joint pathology of the TMJ

Evaluation of the bioequivalence of two formulations containing the combination of 400 mg of acetaminophen (paracetamol), 4 mg of phenylephrine and 4 mg of chlorpheniramine in capsules: open-label, three-way crossover study, partially replicated in healthy volunteers of both sexes

This study was carried out in order to compare the relative bioavailability of two different formulations containing 400 mg of acetaminophen + 4 mg of phenylephrine hydrochloride + 4 mg of chlorpheniramine maleate, Test formulation (Cimegripe®) and Reference formulation (Resfenol®) in 84 healthy volunteers of both sexes under fasting conditions. The study was conducted in a single dose, randomized, open-label, crossover 3-way and partially replicated. The tolerability was evaluated by the monitoring of adverse events and vital signs, results of clinical and laboratory tests. Plasma concentrations were quantified by validated bioanalytical methods using the ultra-performance liquid chromatography coupled to tandem mass spectrometry. The Cmax, Tmax, AUC0-t, AUC0-inf, T1/2 and Kel pharmacokinetic parameters were calculated from these obtained concentrations. The 90% confidence intervals were constructed for the ratio reference/test from the geometric average of the Cmax and AUC parameters which were comprised between 80% and 125%. Only the Cmax parameter of the phenylephrine was applied the scaled average bioequivalence due to the intraindividual coefficient of variation > 30% obtained, thus extending the acceptance limits of the interval. It can be concluded that the two formulations were bioequivalent in terms of rate and absorption extent and thus interchangeable

How healthy are the "Healthy volunteers"? Penetrance of NAFLD in the biomedical research volunteer pool.

Healthy volunteers are crucial for biomedical research. Inadvertent inclusion of subjects with nonalcoholic fatty liver disease (NAFLD) as controls can compromise study validity and subject safety. Given the rising prevalence of NAFLD in the general population, we sought to identify its prevalence and potential impact in volunteers for clinical trials. We conducted a cross-sectional study of subjects who were classified as healthy volunteers between 2011 and 2015 and had no known liver disease. Subjects were classified as presumed NAFLD (pNF; alanine aminotransferase [ALT] level ≥ 20 for women or ≥ 31 for men and body mass index [BMI] > 25 kg/m2 ), healthy non-NAFLD controls (normal ALT and BMI), or indeterminate. A total of 3160 subjects participated as healthy volunteers in 149 clinical trials (1-29 trials per subject); 1732 of these subjects (55%) had a BMI > 25 kg/m2 and 1382 (44%) had abnormal ALT. pNF was present in 881 subjects (27.9%), and these subjects were older than healthy control subjects and had higher triglycerides, low-density lipoprotein cholesterol, and HbA1c and lower high-density lipoprotein cholesterol (P < 0.001 for all). The 149 trials included 101 non-interventional, 33 interventional, and 15 vaccine trials. The impact on study validity of recruiting NAFLD subjects as controls was estimated as likely, probable, and unlikely in 10, 41, and 98 trials, respectively. The proportion of pNF subjects (28%-29%) did not differ by impact. Only 14% of trials used both BMI and ALT for screening. ALT cutoffs for screening were based on local reference values. Grade 3-4 ALT elevations during the study period were rare but more common in pNF subjects than in healthy control subjects (4 versus 1). CONCLUSION: NAFLD is common and often overlooked in volunteers for clinical trials, despite its potential impact on subject safety and validity of study findings. Increased awareness of NAFLD prevalence and stricter ALT cutoffs may ameliorate this problem. (Hepatology 2017;66:825-833).

Efecto de la rigurosidad de las condiciones sobre los resultados de la prueba calórica en sujetos sanos / Effect of the stringency of conditions on caloric test results in healthy subjects

La prueba calórica es una prueba ampliamente utilizada para evaluar la función vestibular, pero las condiciones en las cuales se realiza pueden variar. Se comparó el nistagmo calórico obtenido en 57 sujetos sanos: 24 sujetos estudiados en condiciones ideales y 33 sujetos estudiados en condiciones no ideales. Se observó una disminución estadísticamente significativa de la velocidad de fase lenta en las cuatro irrigaciones realizadas a los sujetos del grupo de condiciones no ideales. Esto debe ser considerado sobre todo al sospechar afectaciones bilaterales. Ser rigurosos en las condiciones permite disminuir el riesgo de diagnóstico erróneo de déficit bilateral (AU)

The caloric test is widely used to assess vestibular function, but the conditions in which it is performed can vary. Caloric nystagmus obtained in 57 healthy subjects were compared: 24 subjects studied in ideal conditions and 33 subjects in non-ideal conditions. A statistically significant decrease in the slow phase velocity of the 4 irrigations performed on the subjects in non-ideal conditions was observed. This must be considered, especially in subjects with suspected bilateral involvement. Stringent conditions reduce the risk of misdiagnosis with bilateral deficit (AU)

Different reference values for hand dynamometry: a conflicting issue / Diferentes valores de referencia para dinamómetro de mano: una cuestión conflictiva

Objective: To identify international normative data sets of handgrip strength (HGS) to be used as reference values in Colombian young and healthy adults. Methods: A prospective and comparative observational study with 294 university students evaluated in an outpatient clinic at the University. Manual dynamometry, weight, height and percentage of body fat were measured. The latter was obtained by measuring 4 skin folds. Results: As expected, it was found that the average maximum manual force obtained from three dynamometric measurements was higher in men than in women. These mean values were very different when compared to those of three populations of the same age obtained in other countries. When classifying subjects with alterations according to their hand strength by dynamometry, the abnormality rates varied considerably. After using a fourth set of values with lower averages than the previous ones, the results were not comparable with those of the population of the present study. The results did not change after adjusting for body mass index and total fat percentage. Conclusions: The values that could have served as reference are not valid to determine the proportion of people with altered hand strength measured by dynamometry in a population of young adults from Colombia. As the usefulness of dynamometry measurements relies upon established and reliable reference values, caution should be taken when using normative data sets from other countries for diagnoses related to hand strength, because global differences can occur. Clinical Relevance: Manual dynamometry is a very useful tool for several professionals related to health and sports. However, it is necessary to have reliable reference values in order to avoid misdiagnosis. For this reason, it is important to have reference values obtained from a population similar to that which will be evaluated, in order to make an accurate diagnosis during the clinical evaluation of patients. manual dynamometry, the dominance of the evaluated subjects must be taken into account, since several sets of reference values from other populations do not report it, and this may be an additional factor for errors. A situation similar to that described in this study may occur in populations in other countries and researchers should ensure that the reference values they use are compatible with their population (AU)

Objetivo: Identificar valores de normalidad de la dinamometría manual a nivel internacional que pudieran servir como referencia en población adulta joven sana de Colombia. Métodos: Estudio observacional prospectivo y comparativo realizado con 294 estudiantes universitarios evaluados en una clínica de consulta externa de la Universidad. Se les midió dinamometría manual, peso, estatura y porcentaje de grasa corporal, éste último mediante la medición de 4 pliegues de grasa subcutánea. Resultados: Como se esperaba, se encontró que el promedio de la fuerza manual máxima obtenida de tres mediciones dinamométricas fue mayor en los hombres que en la mujeres. Estos valores promedio fueron muy diferentes cuando se compararon con los de tres poblaciones de la misma edad obtenidos en otros países. Al categorizar a los sujetos según su fuerza manual mediante dinamometría, los porcentajes de anormalidad variaron considerablemente. Cuando se usó un cuarto conjunto de valores que tenían promedios más bajos que los tres anteriores, los resultados tampoco fueron comparables con los de la población del presente estudio. Menos aún Los resultados no cambiaron luego de realizar ajustes por el índice de masa corporal y el porcentaje total de grasa. Conclusiones: Los valores que podrían haber servido como referencia no son válidos para determinar la proporción de personas con fuerza muscular alterada medida mediante dinamometría manual en una población de jóvenes colombianos. Como la utilidad de las mediciones de dinamometría se basa en valores de referencia establecidos que sean confiables, se debe tener precaución cuando se usen como referencia datos de otros países en diagnósticos relacionados con la fuerza muscular de la mano, ya que existen diferencias significativas a nivel global. Relevancia Clínica: La dinamometría manual es una herramienta muy útil para varios profesionales relacionados con la salud y el deporte. Sin embargo, es necesario contar con valores de referencia confiables con el fin de evitar diagnósticos errados. Es así como se hace necesario obtener valores de referencia obtenidos de una población similar a la que se evaluará con los datos recolectados para favorecer un diagnóstico preciso en la evaluación clínica de los pacientes. Adicionalmente, al construir tablas de valores de referencia para dinamometría manual se debe tener en cuenta la dominancia de los sujetos evaluados ya que varios conjuntos de valores de referencia de otras poblaciones no la reportan y éste puede ser un factor adicional de error. Una situación similar a la descrita en este estudio puede ocurrir en poblaciones de otros países y los investigadores deberían asegurarse de que los valores de referencia que usan sean compatibles con su población (AU)

Comparación del modelo de Cortínez y de Schnider en perfusión de propofol controlada por objetivo de 3 mcg/ml, a biofase, en voluntarios sanos / Comparison of the Cortínez and the Schnider models with a targeted effect-site TCI of 3 mcg/ml in biophase in healthy volunteers

Objetivo. Comparar clínicamente los modelos de Schnider y Cortínez con sistemas «TCI», para la perfusión de propofol a concentración en biofase de 3 mcg/ml en voluntarios sanos. Material y método. Se estudió prospectivamente a 10 voluntarios sanos en 2 ocasiones. Se administró propofol con el modelo de Cortínez o Schnider según asignación aleatorizada. Se compararon tiempos y concentraciones de propofol alcanzadas al momento de pérdida y recuperación de consciencia (LOC y ROC), masa de fármaco administrada, valores de BIS y variables hemodinámicas. El análisis estadístico fue con Wilcoxon pareado. Una p ≤ 0,05 fue considerada significativa. Resultados. El bolo inicial de propofol fue mayor (1,4 [1,3-1,6] versus 0,9 [0,7-1,3] mg/kg; p=0,005) y el LOC ocurrió antes (1,33 [0,67-6,83] versus 3,87 [1,66-11,08] min; p=0,02) con el modelo de Cortínez comparado con el modelo de Schnider. El modelo de Cortínez predice una concentración en biofase al LOC de 2,6mcg/ml (1,65-3,0). Con Schnider, el LOC ocurre 3,87min (1,66-11,8) después de alcanzado el objetivo de 3mcg/ml (p=0,001). Los valores de BIS, las velocidades de perfusión y las variables hemodinámicas fueron similares con ambos modelos a los 20 min de perfusión (p>0,5). La recuperación (ROC) fue más larga con el modelo de Cortínez (11,6 [8,1-16,2] vs. 8,5 [4,7-15,5] min; p=0,003). Conclusiones. El modelo de Cortínez es una buena alternativa al modelo de Schnider para su uso en TCI con objetivo en biofase en sujetos normopeso. Con el objetivo utilizado, las concentraciones en biofase predichas con la Ke0 más lenta incorporada en el modelo de Cortínez permiten discriminar mejor el momento del LOC en la inducción (AU)

Objective. To compare the Cortínez and Schnider models in effect-site TCI mode (3 mcg/ml) in healthy volunteers. Methods. Ten healthy volunteers were prospectively studied on 2 occasions. Propofol was administered with the Cortínez or the Schnider models, as randomly assigned. Times and predicted concentrations at the time of loss and recovery of consciousness (LOC and ROC), mass of drug administered, BIS, and haemodynamic variables were compared. Statistical analysis was with paired Wilcoxon test. A P<.05 was considered significant. Results. The propofol bolo was higher (1.4 [1.3-1.6] versus 0.9 [0.7-1.3] mg/kg, P=.005) and the LOC occurred earlier (1.33 [0.67-6.83] versus 3.87 [1.66-11.08] minutes, P=.02) with the Cortínez model compared to the Schnider model. With the Cortínez model, LOC occurred at an effect site concentrations of 2.6 (1.65-3.0) mcg/ml. With the Schnider model, LOC occurred at 3.87 min (1.66-11.8) after reaching the target of 3 mcg/ml. (P=.001). BIS values, infusion rates, and haemodynamic variables were similar between models after 20minutes of infusion (P>.5). Recovery (ROC) was longer with the Cortínez model (11.6 [8.1-16.2] vs. 8.5 [4.7-15.5] min, P=.003). Conclusions. The Cortínez model is a good alternative to the Schnider model for use in effect-site TCI mode in normal weight subjects. With the target used in this study (3 mcg/ml), the slower Ke0 incorporated into the Cortínez model better discriminated the LOC time (AU)

Guidelines to Classify Female Subject Groups in Sport-Science Research.

AIM: To review current cycling-related sport-science literature to formulate guidelines to classify female subject groups and to compare this classification system for female subject groups with the classification system for male subject groups. METHODS: A database of 82 papers that described female subject groups containing information on preexperimental maximal cycle-protocol designs, terminology, biometrical and physiological parameters, and cycling experience was analyzed. Subject groups were divided into performance levels (PLs), according to the nomenclature. Body mass, body-mass index, maximal oxygen consumption (VO2max), peak power output (PPO), and training status were compared between PLs and between female and male PLs. RESULTS: Five female PLs were defined, representing untrained, active, trained, well-trained, and professional female subjects. VO2max and PPO significantly increased with PL, except for PL3 and PL4 (P < .01). For each PL, significant differences were observed in absolute and relative VO2max and PPO between male and female subject groups. Relative VO2max is the most cited parameter for female subject groups and is proposed as the principal parameter to classify the groups. CONCLUSION: This systematic review shows the large variety in the description of female subject groups in the existing literature. The authors propose a standardized preexperimental testing protocol and guidelines to classify female subject groups into 5 PLs based on relative VO2max, relative PPO, training status, absolute VO2max, and absolute PPO.

Antibiotic susceptibility profile of bacilli isolated from the skin of healthy humans

Abstract In the present work, twelve bacilli were isolated from four different regions of human skin from Bela population of Nagpur district, India. The isolated bacilli were identified by their morphological, cultural and biochemical characteristics. Seven isolates were Gram negative rods, out of which five were belong to genus Pseudomonas. Three among the five Gram positive isolates were identified as Dermabactor and the remaining two Bacillus. Their antimicrobial susceptibility profile was determined by Kirby-Bauer disc diffusion method. The isolates showed resistance to several currently used broad-spectrum antibiotics. The Dermabactor genus was resistant to vancomycin, although it was earlier reported to be susceptible. Imipenem was found to be the most effective antibiotic for Pseudomonas while nalidixic acid, ampicillin and tetracycline were ineffective. Isolates of Bacillus displayed resistance to the extended spectrum antibiotics cephalosporin and ceftazidime. Imipenem, carbenicillin and ticarcillin were found to be the most effective antibiotics as all the investigated isolates were susceptible to them. Antibiotic resistance may be due to the overuse or misuse of antibiotics during the treatment, or following constant exposure to antibiotic-containing cosmetic formulations.

Healthy volunteers can be phenotyped using cutaneous sensitization pain models.

BACKGROUND: Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following repeated measurements. The aim of this study was to determine if the areas of secondary hyperalgesia were consistently robust to be useful for phenotyping subjects, based on their pattern of sensitization by the heat pain models. METHODS: We performed post-hoc analyses of 10 completed healthy volunteer studies (n = 342 [409 repeated measurements]). Three different models were used to induce secondary hyperalgesia to monofilament stimulation: the heat/capsaicin sensitization (H/C), the brief thermal sensitization (BTS), and the burn injury (BI) models. Three studies included both the H/C and BTS models. RESULTS: Within-subject compared to between-subject variability was low, and there was substantial strength of agreement between repeated induction-sessions in most studies. The intraclass correlation coefficient (ICC) improved little with repeated testing beyond two sessions. There was good agreement in categorizing subjects into 'small area' (1(st) quartile [<25%]) and 'large area' (4(th) quartile [>75%]) responders: 56-76% of subjects consistently fell into same 'small-area' or 'large-area' category on two consecutive study days. There was moderate to substantial agreement between the areas of secondary hyperalgesia induced on the same day using the H/C (forearm) and BTS (thigh) models. CONCLUSION: Secondary hyperalgesia induced by experimental heat pain models seem a consistent measure of sensitization in pharmacodynamic and physiological research. The analysis indicates that healthy volunteers can be phenotyped based on their pattern of sensitization by the heat [and heat plus capsaicin] pain models.

Pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers

The pharmacokinetics (PK) of ordinary tablets and sustained release capsules of diltiazem hydrochloride in human clinical trials had been studied. The PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules, a new dosage form, has not been reported, although it is very important to clinical use. In this paper, we investigated the PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules and the food influence in Chinese healthy volunteers. The PK parameters indicated that the diltiazem hydrochloride delay-onset sustained-release pellet capsules appeared marked characteristics of delayed and controlled release. An opened-label, randomized and parallel clinical trial was conducted in 36 Chinese healthy volunteers with single oral dose (90 mg, 180 mg or 270 mg) and a multiple oral dose (90 mg d-1×6 d) administration. The effect of food on the PK of one single oral dose (360 mg) was investigated in 24 healthy Chinese volunteers. Plasma diltiazem concentration was determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and the main pharmacokinetic parameters were analyzed by PKSolver (Ver 2.0). All clinical studies were conducted in the Clinical Pharmacological Center (No. JDX1999064) of Xiangya Hospital Affiliated Central South University, China. The PK parameters suggested that the new formulation had marked characteristics of delayed and controlled release of diltiazem, and food intake did not alter significantly diltiazem pharmacokinetic parameters.

Embora a farmacocinética (PK) do cloridrato de diltiazem nas formas de comprimidos de liberação imediata e cápsulas de liberação modificada em ensaios clínicos já tenha sido relatada, a pesquisa da PK do cloridrato de diltiazem na forma de cápsulas com peletes de liberação retardada e sustentada ainda é muito importante. Neste trabalho, propusemos avaliar a farmacocinética do cloridrato de diltiazem administrado através desta nova forma farmacêutica em voluntários chineses sadios, assim como a influência da ingestão de alimentos neste perfil farmacocinético. Foi realizado um ensaio clínico aberto, randomizado e paralelo em 36 voluntários, que receberam dose oral única de 90 mg, 180 mg ou 270 mg e dose múltiplas (90 mg/d × 6 d) pela mesma via de administração. Para avaliar o efeito da ingestão de alimentos sobre a PK do diltiazem foi realizada a administração de dose única (360 mg) em 24 voluntários chineses sadios. A concentração plasmática do diltiazem foi determinada por Cromatografia Liquida de Alta Eficiência em fase reversa (CLAE-FR) e os principais parâmetros farmacocinéticos foram analisados através do emprego do software PKSolver (Ver 2.0). O ensaio de farmacocinética clínica foi conduzido na clínica Pharmacological Center (No.JDX1999064) do Hospital de Xiangya, Central South University, China. Os parâmetros PK obtidos indicaram que a nova formulação de cápsulas de liberação retardada e sustentada de cloridrato de diltiazem possue marcantes características de liberação retardada e controlada do fármaco.

Methionine enkephalin: immunomodulator in normal volunteers, cancer and AIDS patients

Clinical studies of the immunological effects of methionine enkephalin in normal volunteers, cancer, and AIDS patients are summarized. The major immunology changes seen were increases in T cell subsets, natural killer activity, as well as mitogen blastogenesis. Clinically, the cancer and ARC patients did not develop infections.