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Increased
Dose of Lopinavir/Ritonavir Compensates for Efavirenz-induced Drug-drug
Interaction in HIV Positive Children
Nucleoside
reverse transcriptase inhibitor (NRTI)-sparing regimens
have not yet been systematically evaluated in children.
The non
nucleoside reverse transcriptase inhibitors (NNRTIs)
nevirapine
(Viramune) and efavirenz (Sustiva)
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.
The
aim of the current study was to investigate the pharmacokinetics
of increased-dose (300/75 mg/m twice-daily) lopinavir/ritonavir
with normal-dose (14 mg/kg once-daily) efavirenz in HIV-1-infected
children. 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.
In
conclusion the authors write, “The increased dose of 300/75 mg/m
twice-daily lopinavir/ritonavir compensates for the enzyme-inducing
effect of efavirenz in HIV-infected children.”
Plasma
levels of efavirenz were approximately similar to historical data,
enabling the use of the pediatric standard dose of efavirenz (14
mg/kg once daily). These results suggest that the evaluated doses
of lopinavir/ritonavir and efavirenz are appropriate for most children.
“However,”
the authors note, “regarding the high inter-individual variability
in plasma levels of, in particular, lopinavir, therapeutic drug monitoring
should be applied to identify individual patients who display abnormal
plasma levels.”
05/06/05
Reference
A
S Bergshoeff and others. Journal
of Acquired Immune Deficiency Syndrome 39(1): 63-68. May 1, 2005.
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