Lack of interaction between the HIV integrase inhibitor S/GSK1349572 and tenofovir in healthy subjects

J Acquir Immune Defic Syndr. 2010 Nov;55(3):365-7. doi: 10.1097/QAI.0b013e3181e67909.

Abstract

Background: The potential for a drug interaction between S/GSK1349572 and tenofovir disoproxil fumarate (TDF) was evaluated in an open-label, repeat dose, 3-period, drug-drug interaction study in healthy subjects.

Methods: S/GSK1349572 was administered at 50 mg once daily for 5 days (period 1) followed by a 6-day washout period. TDF 300 mg once daily was then administered for 7 days (period 2). The combination of S/GSK1349572 and TDF was then coadministered for 5 days (period 3). Pharmacokinetic parameters were determined and compared between periods.

Results: Fifteen subjects completed all periods and follow-up. S/GSK1349572 and TDF were generally well tolerated with few adverse events reported. No clinically significant trends in post-dose laboratory abnormalities, vital signs, or electrocardiogram values were noted. Pharmacokinetic parameters of S/GSK1349572 and tenofovir during combination therapy were similar to those when given alone, demonstrating no significant drug interaction. S/GSK1349572 geometric least squares mean ratios (90% confidence interval) for AUC(0-τ), Cmax, and Cτ were 1.01 (0.908, 1.11), 0.969 (0.867, 1.08), and 0.920 (0.816, 1.04), respectively. Tenofovir geometric least squares mean ratios (90% confidence interval) for AUC(0-τ), Cmax, and Cτ were 1.12 (1.01, 1.24), 1.09 (0.974, 1.23), and 1.19 (1.04, 1.35), respectively.

Conclusion: S/GSK1349572 and TDF can be coadministered without dose adjustment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / administration & dosage
  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adenine / pharmacokinetics
  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / pharmacokinetics*
  • Drug Interactions
  • Female
  • HIV Integrase Inhibitors / administration & dosage
  • HIV Integrase Inhibitors / adverse effects
  • HIV Integrase Inhibitors / pharmacokinetics*
  • Human Experimentation
  • Humans
  • Male
  • Middle Aged
  • Organophosphonates / administration & dosage
  • Organophosphonates / adverse effects
  • Organophosphonates / pharmacokinetics*
  • Plasma / chemistry
  • Tenofovir

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Organophosphonates
  • Tenofovir
  • Adenine