Related Experiment Video
Updated: Jun 14, 2025

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
Influence of age and co-medication on dolutegravir glucuronidation in paediatric patients
Tom G Jacobs1, Hylke Waalewijn1,2, Lily Houlden3
1Department of Pharmacy, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, The Netherlands.
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.
Related Concept Videos
Factors Affecting Drug Response: Overview
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...
Phase II Reactions: Glucuronidation
Drug Metabolism: Phase II Reactions
Factors Affecting Drug Biotransformation: Biological
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
Factors Influencing Drug Absorption: Pharmaceutical Parameters

