title: Population analysis of weight-, age-, and sex-related differences in the pharmacokinetics of lopinavir in children from birth to 18 years.
abstract: 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.
authors.affiliation: Service de Pharmacologie Clinique, Groupe Hospitalier Cochin-Saint-Vincent de Paul, 74-82 avenue Denfert-Rochereau, 75674 Paris Cedex 14, France. vincent.jullien@svp.aphp.fr
authors.forename: Vincent
authors.initials: V
authors.lastname: Jullien
authors.forename: Saïk
authors.initials: S
authors.lastname: Urien
authors.forename: Déborah
authors.initials: D
authors.lastname: Hirt
authors.forename: Constance
authors.initials: C
authors.lastname: Delaugerre
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Rey
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Teglas
authors.forename: Paula
authors.initials: P
authors.lastname: Vaz
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chaix
authors.forename: Eugenia
authors.initials: E
authors.lastname: Macassa
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Firtion
authors.forename: Gérard
authors.initials: G
authors.lastname: Pons
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Tréluyer
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000465:Algorithms; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D061466:Lopinavir; D008297:Male; D015233:Models, Statistical; D011153:Population; D011744:Pyrimidinones / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012737:Sex Factors; D013056:Spectrophotometry, Ultraviolet
chemical_list: D019380:Anti-HIV Agents; D011744:Pyrimidinones; D061466:Lopinavir