Joint population pharmacokinetic analysis of zidovudine, lamivudine, and their active intracellular metabolites in HIV patients

HAL Id: inserm-00617423

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Submitted on 17 Nov 2011

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Joint population pharmacokinetic analysis of zidovudine,

lamivudine, and their active intracellular metabolites in

HIV patients

Caroline Bazzoli, Henri Bénech, Elisabeth Rey, Sylvie Retout, Dominique

Salmon, Xavier Duval, Jean-Marc Tréluyer, France Mentré

To cite this version:

Caroline Bazzoli, Henri Bénech, Elisabeth Rey, Sylvie Retout, Dominique Salmon, et al.. Joint pop-ulation pharmacokinetic analysis of zidovudine, lamivudine, and their active intracellular metabolites in HIV patients: Joint population for AZT/AZT-TP and 3TC/3TC-TP. Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2011, 55 (7), pp.3423-3431. �10.1128/AAC.01487-10�. �inserm-00617423�

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Mean metabolic ratio of 3TC (median 51.4) is much larger than the mean metabolic ratio of 5

AZT (median 0.66). The intersubject variability of MMR was 96.8% for AZT and 32.8% for 6

3TC, which is far lower than AZT. 3TC-TP concentrations tended to be higher than AZT-TP 7

concentrations whereas the median mean plasma concentrations in plasma for both parent drugs 8

are in the same range. Using descriptive statistics, Moore et al. (25) found mean 9

intracellular/plasma concentrations ratios of 0.05% and 3%, for AZT and 3TC, respectively. If we 10

compare the MMR of 3TC and AZT by calculating the ratio MMR AZT/MMR 3TC they are in 11

the same range (0.016 and 0.013 in Moore et al. and in this study, respectively). 12

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