ArticleBritish journal of clinical pharmacology2026
Physiologically-based pharmacokinetic modelling of uridine 5'-diphosphoglucorosultransferase (UGT) substrate drugs in pregnant women.
Article in British journal of clinical pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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- Physiologically-based pharmacokinetic modelling of uridine 5'-diphosphoglucorosultransferase (UGT) substrate drugs in pregnant women.British journal of clinical pharmacology · 2026Article
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7 authors.
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Abstract
aimsWhile pregnancy-related changes in phase I enzyme activity are well-documented, less is known about the impact on phase II enzymes. This study aimed to test the hypothesis that changes in the pharmacokinetics (PK) of uridine 5'-diphosphoglucuronosyltransferase (UGT) substrates during pregnancy result from altered enzyme expression or activity. Physiologically based PK (PBPK) modelling was used to evaluate these changes in pregnant populations.
methodsInduction of UGT1A1 and UGT1A4 in pregnancy was modelled using hormone-based equations, which account for the effects of 17β-oestradiol and progesterone. UGT1A3, UGT2B7 and UGT2B15 were assumed unchanged due to a lack of hormone-induced expression. The predicted-to-observed ratio is commonly used to assess the accuracy of PBPK models in predicting clinical data. PBPK model predictions are typically considered acceptable when they fall within a 1.5-fold error, defined as the ratio of the predicted to the observed PK parameter being within a 1.5-fold range.
resultsOverall, 82% of predicted to observed ratio of pregnant population were within 1.5-fold error. P:NP ratios were as follows: UGT1A1: 88%, UGT1A4: 50%, UGT1A9: 100%, UGT2B7: 100%, and UGT2B15: 25%. The P:NP ratio indicates that the PK changes in the pregnant population were successfully predicted for UGT1A1, UGT1A4, UGT1A9 and UGT2B7 substrates.
conclusionsp-PBPK models that incorporated pregnancy-induced changes in UGT1A1, UGT1A4 and UGT1A9 expression/activity, or assumed no change for UGT2B7, accurately predicted the pharmacokinetics of most UGT-metabolized drugs. These findings enhance our understanding of phase II metabolism during pregnancy and may support dose adjustment for those drugs in the future.
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