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© Research
Publication : Antiviral therapy

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Antiviral therapy - 01 Jan 2009

Bouillon-Pichault M, Jullien V, Piketty C, Viard JP, Morini JP, Chhun S, Krivine A, Salmon D, Dupin N, Weiss L, Lortholary O, Pons G, Launay O, Treluyer JM

Link to Pubmed [PMID] – 19918096

Antivir. Ther. (Lond.) 2009;14(7):923-9

BACKGROUND: Lopinavir is a potent protease inhibitor (PI) used for the treatment of HIV infection. Different lopinavir target trough concentrations (C(troughs)) 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 C(troughs) 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 C(troughs) 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 C(trough) 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 C(troughs) 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.

http://www.ncbi.nlm.nih.gov/pubmed/19918096