Pharmacokinetics of lopinavir in HIV type-1-infected children taking the new tablet formulation once daily.
BACKGROUND
Recently, a new tablet formulation of the widely used HIV protease inhibitor lopinavir/ritonavir was licensed. Here, we present a pilot study of the pharmacokinetics of the new adult tablet formulation taken once daily in children.


METHODS
Lopinavir pharmacokinetics of the new adult tablet formulation were evaluated in 15 HIV type-1-infected children between 4 and 15 years of age. A target dose of 460/115 mg/m2 was administered once daily. Plasma concentrations of lopinavir over the course of 24 h were determined with a validated HPLC method.


RESULTS
The median lopinavir dose was 498 mg/m2 (range 424-548). The mean +/- SD for lopinavir area under the 24 h curve was 217.9 +/- 44.9 mg/l x h, the maximum concentration was 14.8 +/- 2.4 mg/l and the concentration 24 h after intake was 3.1 +/- 2.6 mg/l. The half-life of lopinavir was 5.8 +/- 4.5 h and the median time to maximum concentration was 5.8 h (range 1.8-12.2). Overall, the tablet formulation resulted in greater exposure to lopinavir with less variability compared with the soft-gel capsule formulation. All children treated with the new adult tablet formulation had undetectable viral loads (< 50 copies/ml) during 24 weeks follow-up.


CONCLUSIONS
The tablet formulation could probably result in improved lopinavir dosing and increases the feasibility of once-daily lopinavir/ritonavir-based regimens in children.
van der Flier
Michiel
M
Department of Pediatric Infectious Diseases and Immunology, Erasmus Medical Centre, Sophia Children's Hospital, Rotterdam, The Netherlands. m.vanderflier@erasmusmc.nl
Verweel
Gwenda
G
van der Knaap
Linda C
LC
van Jaarsveld
Petronette
P
Driessen
Gert-Jan
GJ
van der Lee
Manon
M
Hartwig
Nico G
NG
Burger
David M
DM
D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000145:classification; D006207:Half-Life; D006801:Humans; D061466:Lopinavir; D008297:Male; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013607:Tablets
D019380:Anti-HIV Agents; D011744:Pyrimidinones; D013607:Tablets; D061466:Lopinavir