Single-dose pharmacokinetics of delavirdine mesylate and didanosine in patients with human immunodeficiency virus infection

G. D. Morse, M. A. Fischl, M. J. Shelton, S. R. Cox, M. Driver, M. Deremer, W. W. Freimuth

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Delavirdine is a nonnucleoside reverse transcriptase inhibitor with in vitro activity against human immunodeficiency virus type 1 (HIV-1) that is currently being evaluated in combination regimens with various nucleoside analogs, including didanosine. Due to the pH-dependent solubility of delavirdine, the buffering agents in didanosine formulations may reduce delavirdine absorption. To evaluate the potential interaction between these agents, 12 HIV-infected patients (mean [± standard deviation] CD4+ cell count, 304 ± 213/mm3) were enrolled in a three-way crossover single-dose study. Didanosine (125 to 200 mg given as buffered tablets) and delavirdine mesylate (400 mg) pharmacokinetics were evaluated when each drug was given alone (treatments A and B, respectively), when the two drugs were given concurrently (treatment C), and when didanosine was given 1 h after delavirdine (treatment D). Delavirdine exposure was reduced by concurrent administration of didanosine. The maximum drug concentration in serum (C(max)) was reduced from 7.22 ± 4.0 to 3.51 ± 1.9 μM, and the area under the concentration-time curve from 0 h to infinity (AUC(0→∞)) was reduced from 22.5 ± 14 to 14 ± 5.7 μM γ h. The extent of N-dealkylation, as indicated by the ratio of the N-dealkylated delavirdine AUC(0→∞) to the delavirdine AUC(0→∞), was unchanged across study treatments (P = 0.708). Reductions in didanosine exposure were observed during concurrent administration with delavirdine with a C(max) reduction from 4.65 ± 2.0 to 3.22 ± 0.59 μM and an AUC(0→∞) reduction from 7.93 ± 3.9 to 6.54 ± 2.3 μM · h. Thus, concurrent administration of delavirdine and didanosine may reduce the AUC(0→∞) of both drugs, although the clinical significance of this reduction is unknown. Administration of delavirdine 1 h before didanosine avoided the interaction. Due to the single-dose nature of this study, these findings require further evaluation at steady state.

Original languageEnglish (US)
Pages (from-to)169-174
Number of pages6
JournalAntimicrobial agents and chemotherapy
Volume41
Issue number1
DOIs
StatePublished - 1997

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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