Increased dose of lopinavir/ritonavir compensates for efavirenz-induced drug-drug interaction in HIV-1-infected children.

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Publication year
2005Source
JAIDS : Journal of Acquired Immune Deficiency Syndromes, 39, 1, (2005), pp. 63-8ISSN
Publication type
Article / Letter to editor

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Organization
Clinical Pharmacy
Radboudumc Extern
Paediatrics - OUD tm 2017
Journal title
JAIDS : Journal of Acquired Immune Deficiency Syndromes
Volume
vol. 39
Issue
iss. 1
Page start
p. 63
Page end
p. 8
Subject
N4i 1: Pathogenesis and modulation of inflammation; N4i 2: Invasive mycoses and compromised host; N4i 3: Poverty-related infectious diseases; N4i 4: Auto-immunity, transplantation and immunotherapy; NCEBP 13: Infectious diseases and international health; UMCN 3.2: Cognitive neurosciences; UMCN 4.1: Microbial pathogenesis and host defenseAbstract
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. CONCLUSION: The increased dose of 300/75 mg/m2 twice-daily lopinavir/ritonavir compensates for the enzyme-inducing effect of efavirenz in HIV-infected children.
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- Academic publications [227864]
- Electronic publications [107342]
- Faculty of Medical Sciences [86218]
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