Population analysis of weight-, age-, and sex-related differences in the pharmacokinetics of lopinavir in children from birth to 18 years.
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.
Jullien
Vincent
V
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
Urien
Saïk
S
Hirt
Déborah
D
Delaugerre
Constance
C
Rey
Elisabeth
E
Teglas
Jean-Paul
JP
Vaz
Paula
P
Rouzioux
Christine
C
Chaix
Marie-Laure
ML
Macassa
Eugenia
E
Firtion
Ghislaine
G
Pons
Gérard
G
Blanche
Stéphane
S
Tréluyer
Jean-Marc
JM
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
D019380:Anti-HIV Agents; D011744:Pyrimidinones; D061466:Lopinavir