RESUMEN
OBJECTIVE: Gender is usually considered to be one of the factors influencing disposition of drugs, but the evidence available is sometimes conflicting and information for a large number of frequently used drugs is lacking. An evaluation of sex differences in the disposition ofmetronidazole was carried out during a bioequivalence study. SUBJECTS AND METHODS: Twenty-four volunteers (12 males and 12 females) were included in an open, single-dose, two-sequence, crossover randomized trial with a one-week washout interval. All volunteers received in each period, a single 250 mg dose of one of the two study formulations of metronidazole. Venous blood samples were collected immediately before and at 15 time points in an 48-hour interval after drug administration; metronidazole concentrations were determined by HPLC. Non-compartmental pharmacokinetic analysis was performed and log-transformed AUC(0-infinity) and Cmax were tested for bioequivalence. Sex differences were evaluated by means of a 4-factor (sex, sequence, treatment and period) ANOVA. RESULTS: The studied formulations were found bioequivalent according to international standards: average 90% confidence interval for AUC(0-infinity) was 98 to 104 and for Cmax 93 to 115. After correction for the administered dose/kg, AUC was about 12% lower in females than in males (p = 0.0388) and, therefore, a higher calculated oral Cl/kg was found in females. Apparent distribution volume, after correction for weight, was significantly higher in males (p = 0.0019). Metronidazole half-life and MRT were shorter in females than in males (p - 0.0014 and p = 0.0002, respectively). CONCLUSIONS: Data obtained in this study suggest that metronidazole clearance in females is about 12% higher than in males although these differences are probably of no clinical relevance.
Asunto(s)
Antiinfecciosos/farmacocinética , Metronidazol/farmacocinética , Adulto , Análisis de Varianza , Antiinfecciosos/sangre , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Femenino , Semivida , Humanos , Masculino , Tasa de Depuración Metabólica , Metronidazol/sangre , Factores Sexuales , Equivalencia TerapéuticaRESUMEN
OBJECTIVE: To test for the bioequivalence of two allopurinol 300 mg tablet formulations (generic allopurinol (Normon) and Zyloric tablets). METHOD: A single dose study was carried out in 24 healthy volunteers with a two-sequence, crossover block-randomized design. Blood samples were taken prior to each administration and at 19 points within 72 h after the dose. Plasma concentrations of allopurinol and oxypurinol were determined by HPLC. The pharmacokinetic parameters Cmax and Tmax were obtained directly from plasma allopurinol and oxypurinol concentrations. ke was estimated by log-linear regression and AUC was calculated by the linear trapezoidal rule for both allopurinol and oxypurinol. The pharmacokinetic parameters AUC and Cmax were tested for equivalence after log-transformation of data. Differences of Tmax were evaluated by a non-parametric test. The 90% standard confidence intervals of the mean values for the test/reference ratios were for AUC and for Cmax, within the acceptable bioequivalence limits of 0.80-1.25 for both allopurinol and oxypurinol. CONCLUSION: The two formulations are bioequivalent and therefore interchangeable.
Asunto(s)
Alopurinol/farmacocinética , Inhibidores Enzimáticos/farmacocinética , Oxipurinol/farmacocinética , Adulto , Alopurinol/administración & dosificación , Área Bajo la Curva , Estudios Cruzados , Inhibidores Enzimáticos/administración & dosificación , Humanos , Masculino , Oxipurinol/administración & dosificación , Comprimidos , Equivalencia TerapéuticaRESUMEN
A bioequivalence study of 2 oral formulations of 500 mg tablets of ciprofloxacin was carried out in 24 healthy volunteers according to a single dose, two-sequence, crossover randomized design. Blood samples were taken prior to each administration and at 13 points within 32 hours after the dose, and plasma concentrations of ciprofloxacin were determined by HPLC. The pharmacokinetic parameters Cmax and tmax were obtained directly from plasma data, ke was estimated by log-linear regression, and AUC was calculated by the trapezoidal rule. The pharmacokinetic parameters AUC and Cmax were tested for bioequivalence after log-transformation of data, differences of tmax were evaluated nonparametrically. The 90% standard confidence intervals of the mean values for the test/reference ratios were 0.87-0.97 for AUC and 0.91-1.05 for Cmax, within the bioequivalence acceptable range of 0.80-1.25 limits. So, we conclude that both formulations were found bioequivalent and, therefore, interchangeable.
Asunto(s)
Antiinfecciosos/farmacocinética , Ciprofloxacina/farmacocinética , Administración Oral , Adulto , Antiinfecciosos/administración & dosificación , Antiinfecciosos/sangre , Área Bajo la Curva , Disponibilidad Biológica , Química Farmacéutica , Ciprofloxacina/administración & dosificación , Ciprofloxacina/sangre , Estudios Cruzados , Humanos , Masculino , España , Equivalencia TerapéuticaRESUMEN
A bioequivalence study of two oral formulations of 300 mg ranitidine was carried out in 16 healthy volunteers (8 men and 8 women), and the pharmacokinetics in both sexes were compared. There was bioequivalence of both formulations. The terminal half-life of ranitidine was 7% shorter and the oral apparent clearance 10.5% higher in women (1.44 L/h/kg) than in men (1.29 L/h/kg), although this difference did not reach statistical significance. No differences were observed in maximum concentration (Cmax) or the time of its occurrence (tmax). Sex, age, and weight did not correlate significantly with oral clearance. These results suggest that there are no sex differences in the pharmacokinetics of ranitidine, or that any differences would not be of clinical relevance. It also should be emphasized that bioequivalence trials also can be used to study other pharmacokinetic or pharmacodynamic characteristics of drugs without damaging the main endpoint of the study.