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Original article

A population analysis of weight-related differences in lopinavir pharmacokinetics and possible consequences for protease inhibitor-naive and -experienced patients

Marion Bouillon-Pichault, Vincent Jullien, Christophe Piketty, Jean-Paul Viard, Jean-Pierre Morini, Stéphanie Chhun, Anne Krivine, Dominique Salmon, Nicolas Dupin, Laurence Weiss, Olivier Lortholary, Gérard Pons, Odile Launay, Jean-Marc Treluyer

Corresponding author name: Vincent Jullien
Corresponding author e-mail: vincent.jullien@svp.aphp.fr

Citation: Antiviral Therapy 2009; 14:923-929
doi: 10.3851/IMP1414

Date accepted: 07 June 2009
Date published online: 11 November 2009

Abstract

Background: Lopinavir is a potent protease inhibitor (PI) used for the treatment of HIV infection. Different lopinavir target trough concentrations (Ctroughs) were previously determined according to patient treatment histories: 1 mg/l for PI-naive patients, and 4 and 5.7 mg/l for PI-experienced patients. However, the probability to achieve these target Ctroughs with the current 400 mg twice-daily or 800 mg once-daily doses of the new tablet form, and the influence of body weight on this probability are unknown.

Methods: A population pharmacokinetic model for lopinavir was developed using data from 424 HIV type-1-infected patients, and the final model was used to estimate the probability to achieve target Ctroughs via Monte Carlo simulations.

Results: A one-compartment model adequately described the data. Mean population estimates (percentage interindividual variability) were 4.61 l/h (36%) for apparent clearance (CL/F) and 63.2 l (70%) for apparent distribution volume. Body weight was found to explain the interindividual variability of lopinavir CL/F. Probability to achieve the 1 mg/l target Ctrough was >96% for the twice-daily dose and comprised between 80% and 90% for the once-daily dose. The probability to achieve the 4 and 5.7 mg/l target Ctroughs with the twice-daily dose significantly decreased when body weight increased (from 76% to 61% and from 56% to 37% respectively, for body weights increasing from 50 to 90 kg).

Conclusions: These results support lopinavir therapeutic drug monitoring and the use of higher lopinavir doses for PI-pretreated patients.

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