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Antimicrobial Agents and Chemotherapy, November 2006, p. 3548-3555, Vol. 50, No. 11
0066-4804/06/$08.00+0     doi:10.1128/AAC.00943-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Population Analysis of Weight-, Age-, and Sex-Related Differences in the Pharmacokinetics of Lopinavir in Children from Birth to 18 Years{triangledown}

Vincent Jullien,1,2,3,5,11* Saïk Urien,6,10,11 Déborah Hirt,1,3,5,11 Constance Delaugerre,1,2,7,9 Elisabeth Rey,1,2,3,5,11 Jean-Paul Teglas,6 Paula Vaz,1,2,8,9 Christine Rouzioux,1,2,7,9,11 Marie-Laure Chaix,1,2,7,9 Eugenia Macassa,1,2,8,9 Ghislaine Firtion,2,4,5 Gérard Pons,1,2,3,5,11 Stéphane Blanche,1,2,8,9,11 and Jean-Marc Tréluyer1,2,3,5,11

Université Paris-Descartes, Faculté de Médecine,1 Assistance Publique-Hôpitaux de Paris,2 Pharmacologie Clinique,3 Gynécologie-Obstétrique 1,4 Groupe Hospitalier Cochin-Saint-Vincent de Paul,5 INSERM,6 Virologie,7 Unité d'Immunologie-Hématologie Pédiatrique,8 Groupe Hospitalier Necker-Enfants Malades,9 Centre René-Huguenin Saint-Cloud,10 EA3620, Paris, France,11

Received 25 July 2005/ Returned for modification 23 November 2005/ Accepted 10 August 2006

The pharmacokinetics of lopinavir were investigated by the use of a population approach performed with the nonlinear mixed effect modeling program NONMEM and 157 children ranging in age from 3 days to 18 years. The pharmacokinetics of lopinavir were well described by a one-compartment model in which the absorption and the elimination rate constants were equal. Typical population estimates of the apparent volume of distribution (V/F) and plasma clearance (CL/F) were 24.6 liters and 2.58 liters/h, respectively. The lopinavir V/F and CL/F were both related to body weight (BW), with an important increase in weight-normalized CL/F for the lowest BW. Combined treatment with lopinavir and nevirapine was found to increase the CL/F. The lopinavir CL/F was also age and sex related, as a 39% increase was observed after the age of 12 years for boys compared to the CL/F for girls. The consequences of these pharmacokinetic discrepancies and the necessity to modify the currently recommended dosage regimen should be further investigated.

* Corresponding author. Mailing address: Service de Pharmacologie Clinique, Groupe Hospitalier Cochin-Saint-Vincent de Paul, 74-82 avenue Denfert-Rochereau, 75674 Paris Cedex 14, France. Phone: 33 1 40488209. Fax: 33 1 40488223. E-mail: vincent.jullien{at}svp.aphp.fr.

{triangledown} Published ahead of print on 28 August 2006.

Antimicrobial Agents and Chemotherapy, November 2006, p. 3548-3555, Vol. 50, No. 11
0066-4804/06/$08.00+0     doi:10.1128/AAC.00943-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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