Jacobs, Tom;
Waalewijn, Hylke;
Houlden, Lily;
Bollen, Pauline;
Nanduudu, Annet;
Nambi, Esether;
Cassim, Haseena;
... Colbers, Angela; + view all
(2024)
Influence of age and co-medication on dolutegravir glucuronidation in paediatric patients.
British Journal of Clinical Pharmacology
, Article e16238. 10.1111/bcp.16238.
(In press).
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Abstract
Dolutegravir (DTG) is primarily metabolized by uridine diphosphate glucuronosyltransferases, forming the pharmacologically inactive DTG glucuronide (DTG-gluc). We described the dolutegravir metabolic ratio (DTG-MR; DTG-gluc AUC0–24h divided by DTG AUC0–24h) in 85 children with HIV aged 3 months to 18 years receiving DTG in the CHAPAS-4 (ISRCTN22964075) and ODYSSEY (NCT02259127) trials. Additionally, we assessed the influence of age, body weight, nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) backbone, rifampicin use and kidney function on DTG-MR. The overall geometric mean (CV%) DTG-MR was 0.054 (52%). Rifampicin use was the only significant factor associated with DTG-MR (P < .001) in multiple linear regression. DTG-MR geometric mean ratio was 1.81 (95% CI: 1.57–2.08) for children while on vs. off rifampicin. This study showed that overall DTG-MR in children was similar to adults, unaffected by age or NRTI backbone, and increased with rifampicin co-administration. These findings support future paediatric pharmacokinetic modelling and extrapolation from adult data.
| Type: | Article |
|---|---|
| Title: | Influence of age and co-medication on dolutegravir glucuronidation in paediatric patients |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/bcp.16238 |
| Publisher version: | https://doi.org/10.1111/bcp.16238 |
| Language: | English |
| Additional information: | Copyright © 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution License, https://creativecommons.org/licenses/by/4.0/, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Children, dolutegravir, drug–drug interaction, glucuronidation, HIV, pharmacokinetics, UGT1A1 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10196632 |
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