Multiple-dose pharmacokinetics of delavirdine mesylate and didanosine in HIV-infected patients

Gene D. Morse*, Susan E. Cohn, Mark J. Shelton, Carol Greisberger, Steven R. Cox, Andrew A. Della-Coletta, William W. Freimuth, Richard C. Reichman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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. Study design and patients: 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 (Cmax) [22.4 ± 11 vs 35.5 ± 17μM; p = 0.045] was noted when delavirdine and didanosine were taken together. However, no significant difference was noted for delavirdine AUC (114 ± 56 μM•h compared with 153 ± 79 μM•h [p = 0.181]). In addition, no differences were noted for didanosine pharmacokinetic parameters between treatments. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)323-328
Number of pages6
JournalClinical Drug Investigation
Volume23
Issue number5
DOIs
StatePublished - 2003

ASJC Scopus subject areas

  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Multiple-dose pharmacokinetics of delavirdine mesylate and didanosine in HIV-infected patients'. Together they form a unique fingerprint.

Cite this