Lopinavir/ritonavir pharmacokinetics in a substitution of high-dose soft-gelatin capsule to tablet formulation

J Clin Pharmacol. 2009 Feb;49(2):155-61. doi: 10.1177/0091270008329550.

Abstract

Guidelines recommend that when soft-gelatin capsules of lopinavir/ritonavir are co-administered with CYP3A4-inducing agents, doses should be increased to 4 capsules (533 mg/133 mg) twice daily. No evidence is available to guide dosing of lopinavir/ritonavir in tablet formulation in this setting. A single-center study is conducted to compare the pharmacokinetics of high-dose lopinavir/ritonavir in 34 patients on stable HAART regimens including 4 soft-gelatin capsules twice daily who then switch to 3 tablets (600 mg/150 mg) twice daily. Median C(min) on soft-gelatin capsule and tablets is 4700 ng/mL (interquartile range [IQR] 2310, 6000 ng/mL) and 5640 ng/mL (IQR 4290, 8080 ng/mL), respectively, for those on inducing agents (n = 17). For patients not on inducing agents (n = 17), median C(min) on soft-gelatin capsule and tablets is 5170 ng/mL (IQR 3640, 6210 ng/mL) and 5640 ng/mL (IQR 4290, 8080 ng/mL), respectively. Among treatment-experienced patients on lopinavir/ritonavir capsules 533/133 mg twice daily, a switch to tablets 600/150 mg twice daily produces comparable pharmacokinetics, regardless of whether they receive concomitant CYP3A4-inducing antiretroviral agents.

Publication types

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

MeSH terms

  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacokinetics
  • Antiretroviral Therapy, Highly Active / methods
  • Capsules
  • Cytochrome P-450 CYP3A / drug effects
  • Cytochrome P-450 CYP3A / metabolism
  • Drug Combinations
  • Drug Therapy, Combination
  • Enzyme Induction / drug effects
  • Female
  • Gelatin / chemistry
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / pharmacokinetics*
  • Humans
  • Lopinavir
  • Male
  • Middle Aged
  • Pyrimidinones / administration & dosage
  • Pyrimidinones / pharmacokinetics*
  • Ritonavir / administration & dosage
  • Ritonavir / pharmacokinetics*
  • Tablets

Substances

  • Anti-HIV Agents
  • Capsules
  • Drug Combinations
  • HIV Protease Inhibitors
  • Pyrimidinones
  • Tablets
  • Lopinavir
  • Gelatin
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Ritonavir