title: Effects of concurrent administration of nevirapine on the disposition of quinine in healthy volunteers.
abstract: OBJECTIVE
  Nevirapine and quinine are likely to be administered concurrently in the treatment of patients with HIV and malaria. Both drugs are metabolised to a significant extent by cytochrome P450 (CYP)3A4 and nevirapine is also an inducer of this enzyme. This study therefore evaluated the effect of nevirapine on the pharmacokinetics of quinine.
  
  
  METHODS
  Quinine (600 mg single dose) was administered either alone or with the 17th dose of nevirapine (200 mg every 12 h for 12 days) to 14 healthy volunteers in a crossover fashion. Blood samples collected at predetermined time intervals were analysed for quinine and its major metabolite, 3-hydroxquinine, using a validated HPLC method.
  
  
  RESULTS
  Administration of quinine plus nevirapine resulted in significant decreases (P < 0.01) in the total area under the concentration-time curve (AUC(T)), maximum plasma concentration (C(max)) and terminal elimination half-life (T((1/2)beta)) of quinine compared with values with quinine dosing alone (AUC: 53.29 +/- 4.01 vs 35.48 +/- 2.01 h mg/l; C(max): 2.83 +/- 0.16 vs 1.81 +/- 0.06 mg/l; T((1/2)beta): 11.35 +/- 0.72 vs 8.54 +/- 0.76 h), while the oral plasma clearance markedly increased (11.32 +/- 0.84 vs 16.97 +/- 0.98 l/h). In the presence of nevirapine there was a pronounced increase in the ratio of AUC(metabolite)/AUC (unchanged drug) and highly significant increases in C(max) and AUC of the metabolite (P < 0.01).
  
  
  CONCLUSIONS
  Nevirapine significantly alters the pharmacokinetics of quinine. An increase in the dose of quinine may be necessary when the drug is co-administered with nevirapine.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria.
authors.forename: Julius O
authors.initials: JO
authors.lastname: Soyinka
authors.forename: Cyprian O
authors.initials: CO
authors.lastname: Onyeji
authors.forename: Sharon I
authors.initials: SI
authors.lastname: Omoruyi
authors.forename: Adegbenga R
authors.initials: AR
authors.lastname: Owolabi
authors.forename: Pullela V
authors.initials: PV
authors.lastname: Sarma
authors.forename: James M
authors.initials: JM
authors.lastname: Cook
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000962:Antimalarials / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage* / Q000627:therapeutic use; D011803:Quinine / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D019380:Anti-HIV Agents; D000962:Antimalarials; D019829:Nevirapine; D011803:Quinine