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Title
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Pharmacokinetics of adjusted-dose 8-hourly lopinavir/ritonavir in HIV-infected children co-treated with rifampicin
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Author
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Abstract
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| Objectives: To evaluate the proportion of children with lopinavir C-min >= 1 mg/L when receiving a novel 8-hourly lopinavir/ritonavir dosing strategy during rifampicin co-treatment. Methods: HIV-infected children on lopinavir/ritonavir and rifampicin were enrolled in a prospective pharmacokinetic study. Children were switched from standard-of-care lopinavir/ritonavir-4:1 with additional ritonavir (1:1 ratio) twice daily to 8-hourly lopinavir/ritonavir-4:1 using weight-banded dosing. Rifampicin was dosed at 10-20 mg/kg/day. After 2 weeks, plasma samples were collected similar to 2, 4, 6, 8 and 10 h after the morning lopinavir/ritonavir-4:1 dose, ALT was obtained to assess safety and treatment was switched back to standard of care. ClinicalTrials.gov registration number: NCT01637558. Results: We recruited 11 children in two weight bands: 5 (45%) were 10-13.9 kg and received 20-24 mg/kg/dose of lopinavir and 6 (55%) children weighed 6-9.9 kg and received 20-23 mg/kg/dose of lopinavir. The median age was 15 months (IQR=12.6-28.8 months). The median (IQR) lopinavir C-min was 3.0 (0.1-5.5) mg/L. Seven (63.6%) of the 11 children had C-min values >= 1 mg/L. Children with a lopinavir mg/kg dose below the median 21.5 were more likely to have C-min <1 mg/L (P=0.02). There was a strong positive correlation between lopinavir and ritonavir concentrations. No associations were found between lopinavir AUC(2-10) and age, sex, weight, nutritional status or mg/kg/dose of lopinavir. Conclusions: These data do not support the use of 8-hourly lopinavir/ritonavir at studied doses. Evaluation of higher doses is needed to optimize treatment outcomes of TB and HIV in young children. |
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Language
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English
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Source (journal)
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The journal of antimicrobial chemotherapy. - London, 1975, currens
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Publication
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London
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2019
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ISSN
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0305-7453
[print]
1460-2091
[online]
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DOI
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10.1093/JAC/DKZ171
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Volume/pages
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74
:8
(2019)
, p. 2347-2351
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ISI
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000483437300035
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Pubmed ID
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31081020
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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