title: Brief report: enzyme inducers reduce elimination half-life after a single dose of nevirapine in healthy women.
abstract: OBJECTIVE
  Single-dose nevirapine (SD-NVP) to prevent mother-to-child transmission (MTCT) of HIV is associated with development of NVP resistance, probably because of its long half-life in combination with a low genetic barrier to resistance. The objective of this study was to find enzyme inducers to reduce the NVP half-life.
  
  
  METHODS
  The design of this phase 1 pharmacokinetic study was a single-center, open-label, 2-period, 9-group study.
  
  
  METHODS
  After administration of a single 200-mg dose of NVP to HIV-seronegative nonpregnant women in periods 1 and 2, blood was sampled twice a week for 21 days. In period 2, additional interventions (single-dose carbamazepine, phenobarbital, or phenytoin; phenytoin for 3 or 7 days; or St. John's wort, vitamin A, or cholecalciferol for 14 days) were administered to all subjects except for the control group.
  
  
  RESULTS
  Thirty-six subjects participated. In 3 intervention groups, the T-half ratio (nevirapine half-life in period 2/half-life in period 1) differed significantly from that in the control group: a single 400-mg dose of carbamazepine (P = 0.021) or 184 mg of phenytoin once daily for 3 (P = 0.021) or 7 days (P = 0.021). The median decreases in the NVP half-life were 18.8, 19.0, and 16.9 hours, respectively.
  
  
  CONCLUSIONS
  Interventions with a single dose of 400 mg of carbamazepine or 184 mg of phenytoin for 3 or 7 days effectively reduced the NVP half-life. Appropriately powered safety and feasibility end point studies are warranted before these interventions can be tested in the setting of single-dose NVP for prevention of mother-to-child transmission (PMTCT) of HIV to reduce the development of NVP resistance.
authors.affiliation: Department of Clinical Pharmacy, Radboud University Medical Centre, Nijmegen, The Netherlands. R.Lhomme@akf.umcn.nl
authors.forename: Rafaëlla F A
authors.initials: RF
authors.lastname: L'homme
authors.forename: Tim
authors.initials: T
authors.lastname: Dijkema
authors.forename: Andre J A M
authors.initials: AJ
authors.lastname: van der Ven
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
mesh_terms: D000293:Adolescent; D000328:Adult; D024882:Drug Resistance, Viral; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006207:Half-Life; D006801:Humans; D019829:Nevirapine / Q000493:pharmacokinetics* / Q000494:pharmacology; D010865:Pilot Projects
chemical_list: D019829:Nevirapine