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.
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-infectedpatients, 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.
Authors: Tim R Cressey; Saik Urien; Edmund V Capparelli; Brookie M Best; Sudanee Buranabanjasatean; Aram Limtrakul; Boonsong Rawangban; Prapan Sabsanong; Jean-Marc Treluyer; Gonzague Jourdain; Alice Stek; Marc Lallemant; Mark Mirochnick Journal: J Antimicrob Chemother Date: 2014-09-25 Impact factor: 5.790
Authors: Keith W Crawford; John Spritzler; Robert C Kalayjian; Teresa Parsons; Alan Landay; Richard Pollard; Vicki Stocker; Michael M Lederman; Charles Flexner Journal: AIDS Res Hum Retroviruses Date: 2010-06 Impact factor: 2.205
Authors: Brookie M Best; Edmund V Capparelli; Huy Diep; Steven S Rossi; Michael J Farrell; Elaine Williams; Grace Lee; John N van den Anker; Natella Rakhmanina Journal: J Acquir Immune Defic Syndr Date: 2011-12-01 Impact factor: 3.731