Concurrent administration of the erythromycin breath test (EBT) and oral midazolam as in vivo probes for CYP3A activity.
Publication/Presentation Date
12-1-1999
Abstract
Given the prominent role of CYP3A in the metabolism of drugs, it is important to identify whether new chemical entities will affect this enzyme system and produce clinically relevant drug interactions. This study evaluated concomitant administration of intravenous [14C N-methyl] erythromycin (3 microCi) (erythromycin breath test; EBT) and 2 mg oral midazolam as probes of systemic and of systemic plus presystemic CYP3A activity, respectively. Twelve males received the probes in a two-period crossover fashion: one period included the probes on two occasions, 5 days apart; in the second period, 200 mg ketoconazole was given orally 2 hours prior to the probes. The within-subject CV for EBT (%14CO2/h) and midazolam AUC0-last was 4.9% and 16.9%, respectively. Ketoconazole reduced %14CO2/h by 43% and increased midazolam AUC0-last by approximately fivefold. In a nonrandomized third period (N = 5), ketoconazole was given simultaneously with midazolam (no EBT); midazolam AUC0-last was similar whether ketoconazole was given 2 hours prior to or simultaneously with the midazolam. The low midazolam dose was generally well tolerated; mild sedation was occasionally seen. Concurrent administration of the EBT and oral midazolam is a sensitive and reproducible tool to screen new chemical entities for potentially important CYP3A interactions.
Volume
39
Issue
12
First Page
1212
Last Page
1220
ISSN
0091-2700
Published In/Presented At
McCrea, J., Prueksaritanont, T., Gertz, B. J., Carides, A., Gillen, L., Antonello, S., Brucker, M. J., Miller-Stein, C., Osborne, B., & Waldman, S. (1999). Concurrent administration of the erythromycin breath test (EBT) and oral midazolam as in vivo probes for CYP3A activity. Journal of clinical pharmacology, 39(12), 1212–1220. https://doi.org/10.1177/00912709922012015
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
10586386
Department(s)
Administration and Leadership
Document Type
Article