Gender differences in the disposition of metronidazole
A.J. Carcas1,2, P. Guerra1, J. Frías1,2, A. Soto1, A. Fernandez-Aijón3, C. Montuenga3, C. Govantes3
1 Centro de Farmacología Clínica, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, 2 Servicio de Farmacología Clínica, Hospital Universitario La Paz, and 3 Departamento de Investigación y Desarrollo, Laboratorios Normon, SA, Madrid, Spain
DOI 10.5414/CPP39213
Abstract
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 of metronidazole 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 AUC0-¥ 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 AUC0-¥ 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 CI/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.
Author Details
Authors
Departments
- 1 Centro de Farmacología Clínica, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid,
- 2 Servicio de Farmacología Clínica, Hospital Universitario La Paz, and
- 3 Departamento de Investigación y Desarrollo, Laboratorios Normon, SA, Madrid, Spain
Address
Dr. A.J. Carcas Sansuán; Farmacología Clínica, Departamento de Farmacología y Terapéutica, Facultad de Medicina, U.A.M., Arzobispo Morcillo s/n, E-28046 Madrid, Spain
Citation
A.J. Carcas, P. Guerra, J. Frías, A. Soto, A. Fernandez-Aijón, C. Montuenga and C. Govantes.Gender differences in the disposition of metronidazole. 2001; 39: 213-218. doi: 10.5414/CPP39213.
