Children with HIV are not small adults: what is different in pharmacology?
OBJECTIVE
The pharmacokinetics of antiretroviral drugs are highly variable among HIV-infected children. This review describes pharmacokinetic processes in children and recent pharmacokinetic data in children with HIV. The general lack of pharmacokinetic data and the potential role of therapeutic drug monitoring are discussed.


RESULTS
It was found unexpectedly that exposure to lopinavir is decreased in the first 6 months of life. Recent findings of subtherapeutic efavirenz concentrations in children suggest that pediatric dose recommendations should be re-evaluated. In addition, recommended dosing of lamivudine leads to lower exposure in children younger than 6 years of age. Preliminary results of pediatric fixed-dose combination tablets for HIV-infected children with a higher nevirapine to stavudine and lamivudine ratio than adult fixed-dose combinations suggest adequate drug exposure. As an alternative to plasma sampling, concentrations of nevirapine can be determined in saliva.


CONCLUSIONS
There is a shortage of pharmacokinetic data in the highly variable population of HIV-infected children. Selected pharmacology studies should be undertaken to improve pediatric dose guidance of existing antiretroviral drugs. Therapeutic drug monitoring is a useful tool to optimize treatment in HIV-infected children. More data are needed, however, to establish child-specific reference values.
Lʼhomme
Rafaëlla
R
aDepartment of Clinical Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands bNijmegen University Centre for Infectious diseases (NUCI), Nijmegen, The Netherlands cDepartment of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands dMedical Research Council, Clinical Trials Unit, London, UK.
Warris
Adilia
A
Gibb
Diana
D
Burger
David
D