Pharmacokinetic interaction between amprenavir and delavirdine: evidence of induced clearance by amprenavir

Clin Pharmacol Ther. 2002 Dec;72(6):615-26. doi: 10.1067/mcp.2002.128868.


Objective: Our objective was to determine the pharmacokinetic interaction between amprenavir and delavirdine.

Methods: Healthy volunteers participated in 2 open-label, 3-period, longitudinal studies. In the first study, 12 volunteers received a single dose of amprenavir, 1200 mg, alone and then again after 7 days of delavirdine, 600 mg twice daily. In the second study, another 12 subjects received amprenavir, 1200 mg twice daily, alone for 7 days. After a 7-day washout period, subjects received delavirdine, 600 mg twice daily, alone for 7 days followed by a combination with amprenavir, 600 mg twice daily, for another 7 days. Amprenavir and delavirdine pharmacokinetics when given alone and in combination were compared.

Results: All 12 subjects completed the first study, and 11 subjects completed the second study. Delavirdine significantly increased the area under the curve (AUC) of single-dose amprenavir by 4-fold (P =.0001). Amprenavir, 600 mg twice daily, with delavirdine produced higher levels of amprenavir AUC, minimum concentration (C(min)), and maximum concentration (C(max)), by 30%, 90%, and 18%, respectively, than those of amprenavir, 1200 mg twice daily, alone (P <.05). In contrast, amprenavir decreased delavirdine AUC, C(min), and C(max) by 50%, 70%, and 30%, respectively (P <.005).

Conclusions: Because of the inhibitory effect of delavirdine on the cytochrome P450 3A4-mediated metabolism of amprenavir, the combination of a reduced dose of amprenavir, 600 mg twice daily, with delavirdine resulted in a higher amprenavir exposure than the standard dose of amprenavir, 1200 mg twice daily. However, amprenavir induced the clearance of delavirdine, resulting in a reduction in delavirdine exposure. Further clinical studies are needed to determine the appropriate dosing regimens for delavirdine and amprenavir during coadministration.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / blood
  • Anti-HIV Agents / pharmacokinetics*
  • Antiretroviral Therapy, Highly Active
  • Area Under Curve
  • Carbamates
  • Delavirdine / administration & dosage
  • Delavirdine / blood
  • Delavirdine / pharmacokinetics*
  • Drug Administration Schedule
  • Drug Interactions
  • Female
  • Furans
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Reference Values
  • Sulfonamides / administration & dosage
  • Sulfonamides / blood
  • Sulfonamides / pharmacokinetics*


  • Anti-HIV Agents
  • Carbamates
  • Furans
  • Sulfonamides
  • amprenavir
  • Delavirdine