Increased dose of lopinavir/ritonavir compensates for efavirenz-induced drug-drug interaction in HIV-1-infected children.
BACKGROUND
Nucleoside reverse transcriptase inhibitor-sparing regimens have not yet been systematically evaluated in children. The nonnucleoside reverse transcriptase inhibitors nevirapine and efavirenz lower plasma levels of protease inhibitors in adults and children. Therefore, coadministration of lopinavir/ritonavir with nevirapine and efavirenz necessitates a 30% increase in the dose of lopinavir/ritonavir in adults. In children, the extent of the pharmacokinetic interaction between efavirenz and lopinavir/ritonavir has not yet been studied.


OBJECTIVE
To investigate the pharmacokinetics of increased-dose (300/75 mg/m2 twice-daily) lopinavir/ritonavir with normal-dose (14 mg/kg once-daily) efavirenz in HIV-1-infected children.


METHODS
Steady-state pharmacokinetics of lopinavir and efavirenz were determined and compared with historical data.


RESULTS
Fifteen children of median age 11.8 (range, 5.7-16.3) years were included. Area under the plasma concentration-time curve (AUC0-12), peak levels (Cmax), and trough levels (Cmin) of lopinavir were similar to historical data in adults and children. Medians (interquartile range) were 92.3 (43.5-138.5) mg/L.h, 12.5 (6.9-16.7) mg/L, and 5.7 (1.3-8.0) mg/L, respectively. Efavirenz pharmacokinetics approximated previous data in adults and children.


CONCLUSIONS
The increased dose of 300/75 mg/m2 twice-daily lopinavir/ritonavir compensates for the enzyme-inducing effect of efavirenz in HIV-infected children.
Bergshoeff
Alina S
AS
Department of Clinical Pharmacy, University Medical Center, 6500 HB Nijmegen, The Netherlands.
Fraaij
Pieter L
PL
Ndagijimana
Jennifer
J
Verweel
Gwenda
G
Hartwig
Nico G
NG
Niehues
Tim
T
De Groot
Ronald
R
Burger
David M
DM
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D019540:Area Under Curve; D048588:Benzoxazines; D002648:Child; D002675:Child, Preschool; D003521:Cyclopropanes; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D061466:Lopinavir; D008297:Male; D010078:Oxazines / Q000009:adverse effects / Q000493:pharmacokinetics*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012449:Safety
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D010078:Oxazines; D011744:Pyrimidinones; D061466:Lopinavir; C098320:efavirenz; D019438:Ritonavir