title: Gender differences in the disposition of metronidazole.
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 ofmetronidazole was carried out during a bioequivalence study.
  
  
  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.
authors.affiliation: Centro de Farmacologia Clinica, Departamento de Farmacologia y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
authors.forename: A J
authors.initials: AJ
authors.lastname: Carcas
authors.forename: P
authors.initials: P
authors.lastname: Guerra
authors.forename: J
authors.initials: J
authors.lastname: Frias
authors.forename: A
authors.initials: A
authors.lastname: Soto
authors.forename: A
authors.initials: A
authors.lastname: Fernandez-Aijón
authors.forename: C
authors.initials: C
authors.lastname: Montuenga
authors.forename: C
authors.initials: C
authors.lastname: Govantes
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008795:Metronidazole / Q000097:blood / Q000493:pharmacokinetics*; D012737:Sex Factors; D013810:Therapeutic Equivalency
chemical_list: D000890:Anti-Infective Agents; D008795:Metronidazole