Faculty Collaboration Database

Limitations of using a single postdose midazolam concentration to predict CYP3A-mediated drug interactions. J Clin Pharmacol 2008 Jun;48(6):671-80

Date

04/19/2008

Pubmed ID

18420532

Pubmed Central ID

PMC2658757

DOI

10.1177/0091270008317305

Scopus ID

2-s2.0-44049088374 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

Midazolam is a common probe used to predict CYP3A activity, but multiple blood samples are necessary to determine midazolam's area under the concentration-time curve (AUC). As such, single sampling strategies have been examined. The purpose of this study was to assess the ability of single midazolam concentrations to predict midazolam AUC in the presence and absence of CYP3A modulation by Ginkgo biloba extract (GBE). Subjects received oral midazolam 8 mg before and after 28 days of GBE administration. Postdose blood samples were collected during both study periods and midazolam AUC determined. Linear regression was used to generate measures of predictive performance for each midazolam concentration. The geometric mean ratio (90% confidence intervals) of midazolam AUC(0-infinity) post-GBE/AUC(0-infinity) pre-GBE was 0.66 (0.49-0.84) (P = .03). Before and after GBE administration, optimal midazolam sampling times were identified at 3.5 to 5 hours and 2 to 3 hours, respectively. Single midazolam concentrations between 2 and 5 hours correctly predicted the reduction in midazolam AUC following GBE exposure, but confidence intervals were generally wide. Intersubject variability in CYP3A activity (either inherent or from drug administration) alters the prediction of optimal midazolam sampling times; therefore, midazolam AUC is preferred for assessing CYP3A activity in drug-drug interaction studies.

Author List

Penzak SR, Busse KH, Robertson SM, Formentini E, Alfaro RM, Davey RT Jr

Author

Kristin Busse PharmD Assistant Professor in the School of Pharmacy Administration department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Administration, Oral
Adult
Area Under Curve
Cytochrome P-450 CYP3A
Female
Forecasting
Ginkgo biloba
Herb-Drug Interactions
Humans
Linear Models
Longitudinal Studies
Male
Midazolam
Middle Aged
Plant Extracts
Time Factors