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Abacavir Pharmacokinetics in Human Immunodeficiency Virus–Infected Children Ranging in Age From 1 Month to 16 Years: A Population Analysis

From Pharmacologie Clinique, Université René Descartes, Groupe Hospitalier Cochin-Saint-Vincent-de-Paul, Assistance Publique-Hôpitaux de Paris, Paris, France (Dr Jullien, Dr Urien, Dr Chappuy, Dr Dimet, Dr Rey, Dr Pons, Dr Tréluyer) and Hématologie Pédiatrique, Hôpital Necker-Enfants-Malades, Assistance Publique-Hôpitaux de Paris, Paris, France (Dr Blanche).

Abacavir pharmacokinetics was studied in 105 children by a population approach performed with NONMEM. A 1-compartment open model with linear absorption and elimination adequately described the data. Typical population estimates (percent interindividual variability) of absorption rate constant, apparent distribution volume, and apparent plasma clearance were 1.79 h^–1 (58%), 42.9 L (53%), and 24.3 L/h (30%), respectively. Apparent plasma clearance was positively related to body weight. Individual Bayesian estimates of apparent plasma clearance were used to calculate individual abacavir area under the concentration curve (AUC). For the current weight-based regimen, abacavir exposure was found to be constant throughout the age range of the study, with an overall mean AUC value of 8.5 ± 2.5 mg·h/L, which is slightly greater than the mean AUC value reported in adults. This study confirms the relevance of the current weight-based abacavir dosage regimen in pediatric patients.

Key Words: Human immunodeficiency virus (HIV) • abacavir • children • body weight • population pharmacokinetics

Address for reprints: Vincent Jullien, Pharmacologie Clinique, Université René Descartes, Groupe Hospitalier Cochin-Saint-Vincent-de-Paul, Assistance Publique-Hôpitaux de Paris, 82 Avenue Denfert-Rochereau, 75674 Paris Cedex 14, France.

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