title: A comparison of the steady-state pharmacokinetics of nevirapine in men, nonpregnant women and women in late pregnancy.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics of nevirapine and any possible influencing factors in pregnant women (n = 16), nonpregnant women (n = 13) and men (n = 14), who received nevirapine 200 mg twice daily together with nucleoside reverse transcriptase inhibitors.
  
  
  METHODS
  Blood samples were taken for 12 h at steady state. Nevirapine concentrations were measured by liquid chromatography-tandem mass spectrometry. The influence of gender, age, body weight and comedication on minimum and maximum concentrations (C(min), C(max)), area under the concentration-time curve (AUC), total clearance (CL(tot)), half-life (t(1/2)) and volume of distribution (V(d)) was analysed by multivariate techniques.
  
  
  RESULTS
  Mean [95% confidence interval (CI)]C(max), AUC(ss) and clearance were 5221 ng ml(-1) (4267, 6175), 50 789 ng (-1)h ml(-1) (43 453, 58 125) and 69.9 ml min(-1) for men, 5871 ng ml(-1) (4848, 6895), 57 045 ng h(-1) ml(-1) (45 997, 68 093) and 65.6 ml min(-1) for nonpregnant women and 4505 ng ml(-1) (3644, 5366), 44 579 ng h(-1) ml(-1) (36 564, 52 594) and 82.1 ml min(-1) for pregnant women. The differences between pregnant and nonpregnant women (% difference, 95% CI) in C(max) (-30.3; -28.5, -33.0), AUC(ss) (-28.0; - 25.8, - 29.5) and clearance (20.2; 26.6, 15.6) reached statistical significance (P = 0.010, P = 0.028 and P = 0.028, respectively). The multivariate analysis underscored the influence of bodyweight on the plasma exposure to nevirapine.
  
  
  CONCLUSIONS
  Pregnant women exhibited an increased nevirapine clearance and comparably low plasma concentrations, whereas women with a low bodyweight achieved high plasma nevirapine concentrations. The large variability in nevirapine concentrations in women may lead to loss of efficacy and viral resistance, or drug toxicity, and therefore these patients should be monitored frequently.
authors.affiliation: Pharmazentrum Frankfurt at the JW Goethe University, Frankfurt, Germany. hentig@em.uni-frankfurt.de
authors.forename: Nils
authors.initials: N
authors.lastname: von Hentig
authors.forename: Amina
authors.initials: A
authors.lastname: Carlebach
authors.forename: Peter
authors.initials: P
authors.lastname: Gute
authors.forename: Gaby
authors.initials: G
authors.lastname: Knecht
authors.forename: Stefan
authors.initials: S
authors.lastname: Klauke
authors.forename: Maren
authors.initials: M
authors.lastname: Rohrbacher
authors.forename: Hartmut
authors.initials: H
authors.lastname: Stocker
authors.forename: Michael
authors.initials: M
authors.lastname: Kurowski
authors.forename: Sebastian
authors.initials: S
authors.lastname: Harder
authors.forename: Schlomo
authors.initials: S
authors.lastname: Staszewski
authors.forename: Annette
authors.initials: A
authors.lastname: Haberl
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011263:Pregnancy Trimester, Third; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine