Journal article
Physiologically Based Pharmacokinetic Modeling Framework for Quantitative Prediction of an Herb–Drug Interaction
CPT: pharmacometrics and systems pharmacology, Vol.3(3), pp.e107-9
03/2014
Handle:
https://hdl.handle.net/2376/113591
PMCID: PMC4042458
PMID: 24670388
Abstract
Herb–drug interaction predictions remain challenging. Physiologically based
pharmacokinetic (PBPK) modeling was used to improve prediction accuracy of potential
herb–drug interactions using the semipurified milk thistle preparation, silibinin,
as an exemplar herbal product. Interactions between silibinin constituents and the probe
substrates warfarin (CYP2C9) and midazolam (CYP3A) were simulated. A low silibinin dose
(160 mg/day × 14 days) was predicted to increase midazolam area under the
curve (AUC) by 1%, which was corroborated with external data; a higher dose
(1,650 mg/day × 7 days) was predicted to increase midazolam and
(
S
)-warfarin AUC by 5% and 4%, respectively. A proof-of-concept clinical study
confirmed minimal interaction between high-dose silibinin and both midazolam and
(
S
)-warfarin (9 and 13% increase in AUC, respectively). Unexpectedly,
(
R
)-warfarin AUC decreased (by 15%), but this is unlikely to be clinically
important. Application of this PBPK modeling framework to other herb–drug
interactions could facilitate development of guidelines for quantitative prediction of
clinically relevant interactions.
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Details
- Title
- Physiologically Based Pharmacokinetic Modeling Framework for Quantitative Prediction of an Herb–Drug Interaction
- Creators
- S J Brantley - , Chapel Hill, North CarolinaB T Gufford - , Spokane, WashingtonR Dua - , Chapel Hill, North CarolinaD J Fediuk - , Chapel Hill, North CarolinaT N Graf - , Greensboro, North CarolinaY V Scarlett - , Chapel Hill, North CarolinaK S Frederick - , Ridgefield, ConnecticutM B Fisher - , Oxford, ConnecticutN H Oberlies - , Greensboro, North CarolinaM F Paine - , Spokane, Washington
- Publication Details
- CPT: pharmacometrics and systems pharmacology, Vol.3(3), pp.e107-9
- Academic Unit
- Pharmaceutical Sciences, Department of
- Publisher
- Nature Publishing Group
- Identifiers
- 99900547555901842
- Language
- English
- Resource Type
- Journal article