title: Multiple-Dose Pharmacokinetics of Delavirdine Mesylate and Didanosine in HIV-Infected Patients.
abstract: BACKGROUND
  Delavirdine is a non-nucleoside reverse transcriptase inhibitor with pH-dependent absorption characteristics that has received accelerated approval for the treatment of patients with HIV-1 infection. In a prior single-dose study concurrent administration of delavirdine mesylate and didanosine (buffered formulation) resulted in up to a 31% decrease in the area under the plasma delavirdine concentration versus time curve (AUC) compared with when both drugs were taken separately.
  
  
  OBJECTIVE
  To evaluate the interaction of these two agents at steady state.
  
  
  METHODS
  A total of 11 HIV-infected subjects who were previously stabilised on didanosine were enrolled into a randomised, open-labelled crossover study. Nine subjects continued to receive their prescribed dose and schedule of didanosine, with each dose of didanosine taken either together with or 1 hour after delavirdine mesylate (400mg every 8 hours). Pharmacokinetic studies at baseline, day 14 and day 28 were conducted and the plasma concentrations of delavirdine and didanosine were determined.
  
  
  RESULTS
  A lower delavirdine maximum plasma concentration (C(max)) [22.4 +/- 11 vs 35.5 +/- 17muM; p = 0.045] was noted when delavirdine and didanosine were taken together. However, no significant difference was noted for delavirdine AUC (114 +/- 56 muM.h compared with 153 +/- 79 muM.h [p = 0.181]). In addition, no differences were noted for didanosine pharmacokinetic parameters between treatments.
  
  
  CONCLUSIONS
  These data indicate that patients receiving didanosine and delavirdine as part of a combination regimen during long-term therapy can be instructed to take them together in an attempt to enhance adherence to treatment with both antiretroviral agents.
authors.affiliation: Laboratory for Antiviral Research, Department of Pharmacy Practice, University at Buffalo, Buffalo, New York, USA.
authors.forename: Gene D
authors.initials: GD
authors.lastname: Morse
authors.forename: Susan E
authors.initials: SE
authors.lastname: Cohn
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shelton
authors.forename: Carol
authors.initials: C
authors.lastname: Greisberger
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cox
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Della-Coletta
authors.forename: William W
authors.initials: WW
authors.lastname: Freimuth
authors.forename: Richard C
authors.initials: RC
authors.lastname: Reichman