title: Lack of a pharmacokinetic drug-drug interaction with venlafaxine extended-release/indinavir and desvenlafaxine extended-release/indinavir.
abstract: OBJECTIVE
  To assess the effects of venlafaxine extended-release (XR) capsules and desvenlafaxine extended-release (XR) tablets upon indinavir pharmacokinetic properties when co-administrated to healthy volunteers.
  
  
  METHODS
  This was an open-label, two-period, fixed-dose study conducted at the clinical research unit located on a university campus. Twenty-four healthy volunteers enrolled in the study (mean age 28.3 ± 8.0 years). Each subject received a single dose of indinavir 800 mg on day 1. Subsequently, subjects were then randomly assigned to either the venlafaxine XR group (N = 12) or the desvenlafaxine XR group (N = 12). Starting on day 2, venlafaxine XR was dosed at 37.5 mg/day for 4 days and increased to 75 mg/day for 6 days. Desvenlafaxine XR was dosed at 50 mg/day for 10 days. On day 12, indivanvir 800 mg was co-administered to both the venlafaxine XR and the desvenlafaxine XR groups. The pharmacokinetics of indinavir were determined both before and at the end of antidepressant dosing. Plasma indinavir, venlafaxine, and desvenlafaxine concentrations were assayed by high-performance liquid chromatography with ultra-violet (UV) detection. Indinavir pharmacokinetic parameters were calculated by noncompartmental analysis using validated computer software.
  
  
  RESULTS
  Venlafaxine XR and desvenlafaxine XR did not produce any significant changes in indinavir disposition. Both antidepressants were well tolerated by the subjects with only minor adverse side effects.
  
  
  CONCLUSIONS
  No pharmacokinetic drug-drug interaction was demonstrated between venlafaxine XR and indinavir or between desvenlafaxine XR and indinvair. The lack of interaction could be due to the venlafaxine and desvenlafaxine extended-release formulation.
authors.affiliation: Mercer University College of Pharmacy and Health Sciences, 3001 Mercer University Dr., Atlanta, GA 30341, USA. jann_mw@mercer.edu
authors.forename: Michael W
authors.initials: MW
authors.lastname: Jann
authors.forename: Vicky
authors.initials: V
authors.lastname: Spratlin
authors.forename: Kathryn
authors.initials: K
authors.lastname: Momary
authors.forename: Hailing
authors.initials: H
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Turner
authors.forename: Scott R
authors.initials: SR
authors.lastname: Penzak
authors.forename: Alan
authors.initials: A
authors.lastname: Wright
authors.forename: Chad
authors.initials: C
authors.lastname: VanDenBerg
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D002214:Capsules; D003511:Cyclohexanols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D000069468:Desvenlafaxine Succinate; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D013607:Tablets; D000069470:Venlafaxine Hydrochloride; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D002214:Capsules; D003511:Cyclohexanols; D003692:Delayed-Action Preparations; D000069468:Desvenlafaxine Succinate; D017320:HIV Protease Inhibitors; D019469:Indinavir; D017367:Selective Serotonin Reuptake Inhibitors; D013607:Tablets; D000069470:Venlafaxine Hydrochloride