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. 2005 Feb;59(2):183-8.
doi: 10.1111/j.1365-2125.2004.02259.x.

Weight related differences in the pharmacokinetics of abacavir in HIV-infected patients

V Jullien  1 , J-M Tréluyer, H Chappuy, J Dimet, E Rey, N Dupin, D Salmon, G Pons, S Urien
Affiliations

Weight related differences in the pharmacokinetics of abacavir in HIV-infected patients

V Jullien et al. Br J Clin Pharmacol. 2005 Feb.

Abstract

Aim: To study the possible influence of patient characteristics on abacavir pharmacokinetics.

Methods: A population pharmacokinetic model for abacavir was developed using data from 188 adult patients by the use of a nonlinear mixed effects modelling method performed with NONMEM.

Results: Abacavir pharmacokinetics was well described by a two-compartment open model with linear absorption and elimination. Typical population estimates for the absorption rate constant (Ka), the apparent central distribution volume (Vc/F), the apparent peripheral distribution volume (Vp/F), the apparent intercompartmental clearance (Q/F) and the apparent plasma clearance (CL/F) were 1.8 h(-1), 75 l, 23.6 l, 10 l h(-1) and 47.5 l h(-1), respectively. Apparent plasma clearance was positively related to bodyweight. Individual Bayesian estimates of CL/F were used to calculate abacavir AUC. The latter decreased from 10.7 +/- 5.0 to 5.7 +/- 1.6 mgh l(-1) when bodyweight increased from 36 to 102 kg. This drop in abacavir exposure could lead to suboptimal treatment for the heaviest patients, as antiviral efficacy of abacavir is known to be related to its AUC. A 400 mg abacavir dose would be necessary to achieve adequate exposure to abacavir in patients weighing more than 60 kg.

Conclusions: The apparent plasma clearance of abacavir was positively related to bodyweight. The efficacy of the current recommended abacavir dosage for patients with high bodyweight should be evaluated in further studies.

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Figures

Figure 1
Figure 1
Observed abacavir concentrations vs. time data and the typical curve
Figure 2
Figure 2
(A) Goodness of fit evaluated by weighted residuals (WRES) vs. time data; (B) WRES vs. model predicted (PRED) plasma abacavir concentrations
Figure 3
Figure 3
(A) Abacavir exposure achieved for a 300 mg BID dose in the 188 adult patients. Mean ± standard deviation (SD) of AUC vs. bodyweight (BW); (B) percentage of patient reaching the 6 mg h l−1 AUC value thought to correspond to the beginning of the plateau phase of abacavir antiviral efficacy vs. bodyweight. anova: •P < 0.001 vs. < 50 kg BW group; □P < 0.01 vs. 50–60 kg BW group; ▪P < 0.1 vs. 50–60 kg BW group; n: number of subjects per BW group
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