Plasma concentrations of generic lopinavir/ritonavir in HIV type-1-infected individuals

Antivir Ther. 2009;14(7):1001-4. doi: 10.3851/IMP1410.

Abstract

Background: Generic drugs can contribute to access to treatment for HIV-infected patients. However quality and safety remains an issue of concern. Therefore, we evaluated minimal plasma concentrations and short-term safety of a generic lopinavir/ritonavir 200/50 mg tablet formulation.

Methods: In a single-centre prospective pilot study, patients receiving protease-inhibitor-based antiretroviral treatment were switched to a generic lopinavir/ritonavir tablet at the standard dose (400/100 mg twice daily). Minimum drug concentrations (C(min)) of lopinavir and ritonavir were performed before switching (in 16 patients who were on Kaletra((R)) soft-gel capsules) and after 4 weeks (in all patients). Plasma levels of lopinavir and ritonavir were determined by a validated HPLC method. Either the Wilcoxon signed-rank or Mann-Whitney U test was used to compare the groups.

Results: A total of 37 patients (18 females) were included in the study. Two stopped their study medications prematurely because of intolerance. The median (interquartile range) lopinavir C(min) was 7.2 mg/l (5.8-8.3) and no patients had subtherapeutic levels <1.0 mg/l. No significant difference of lopinavir C(min) levels was found between Kaletra((R)), and the generic product (P=0.224). By contrast, the C(min) of generic ritonavir was higher (P=0.012). Food did not affect the drug levels. Mild gastrointestinal complaints were reported in 12 patients.

Conclusions: The generic lopinavir/ritonavir tablet showed C(min) plasma concentrations similar to what is described for the branded product, with good stability, independent of food intake. These data support the efforts in scaling up access to generic second-line treatment in middle- and low-income countries.

Trial registration: ClinicalTrials.gov NCT00802334.

Publication types

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

MeSH terms

  • Adult
  • Drug Administration Schedule
  • Drug Combinations
  • Drugs, Generic / administration & dosage
  • Drugs, Generic / pharmacokinetics*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism
  • HIV Infections / virology
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / blood
  • HIV Protease Inhibitors / pharmacokinetics*
  • HIV-1 / drug effects*
  • Humans
  • Lopinavir
  • Male
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Pyrimidinones / administration & dosage
  • Pyrimidinones / blood
  • Pyrimidinones / pharmacokinetics*
  • Ritonavir / administration & dosage
  • Ritonavir / blood
  • Ritonavir / pharmacokinetics*
  • Tablets / administration & dosage
  • Tablets / pharmacokinetics

Substances

  • Drug Combinations
  • Drugs, Generic
  • HIV Protease Inhibitors
  • Pyrimidinones
  • Tablets
  • Lopinavir
  • Ritonavir

Associated data

  • ClinicalTrials.gov/NCT00802334