Publication
Title
Pharmacokinetics and safety of rifabutin in young HIV-infected children receiving rifabutin and lopinavir/ritonavir
Author
Abstract
Objectives: Co-treatment of HIV and TB in young children is complicated by limited treatment options and complex drug-drug interactions. Rifabutin is an alternative to rifampicin for adults receiving a ritonavir-boosted PI. We aimed to evaluate the short-term safety and pharmacokinetics of rifabutin when given with lopinavir/ritonavir in children. Patients and methods: We conducted an open-label study of rifabutin dosed at 5 mg/kg three times a week in HIV-infected children <= 5 years of age receiving lopinavir/ritonavir. Intensive steady-state pharmacokinetic sampling was conducted after six doses. The Division of AIDS 2004, clarification 2009, table for grading severity of adverse events was used to classify drug toxicities. The study was registered with ClinicalTrials.gov, number NCT01259219. Results: Six children completed the study prior to closure by institutional review boards. The median (range) AUC(0-48) of rifabutin was 6.91 (3.52-8.67) mu g.h/mL, the median (range) C-max of rifabutin was 0.39 (0.19-0.46) mu g/mL, the median (range) AUC(0-48) of 25-O-desacetyl rifabutin was 5.73 (2.85-9.13) mu g.h/mL and the median (range) C-max of 25-O-desacetyl rifabutin was 0.17 (0.08-0.32) mg/mL. The neutrophil count declined in all children; two children experienced grade 4 neutropenia, which resolved rapidly without complications. There was strong correlation between AUC(0-48) measures and neutrophil counts. Conclusions: Rifabutin dosed at 5 mg/kg three times per week resulted in lower AUC(0-48), AUC(0-24) and C-max values for rifabutin and 25-O-desacetyl rifabutin compared with adults receiving 150 mg of rifabutin daily, the current recommended dose. We observed high rates of severe transient neutropenia, possibly due to immaturity of CYP3A4 in young children. It remains unclear whether a safe and effective rifabutin dose exists for treatment of TB in children receiving lopinavir/ritonavir.
Language
English
Source (journal)
The journal of antimicrobial chemotherapy. - London, 1975, currens
Publication
London : 2015
ISSN
0305-7453 [print]
1460-2091 [online]
DOI
10.1093/JAC/DKU382
Volume/pages
70 :2 (2015) , p. 543-549
ISI
000350211600026
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
External links
Web of Science
Record
Identifier
Creation 15.02.2018
Last edited 25.02.2023
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