Simvastatin does not affect CYP3A activity, quantified by the erythromycin breath test and oral midazolam pharmacokinetics, in healthy male subjects.
Publication/Presentation Date
11-1-2000
Abstract
Potential for inhibition of CYP3A activity by simvastatin, an HMG-CoA reductase inhibitor, was evaluated in 12 healthy male subjects who received placebo or 80 mg of simvastatin, the maximal recommended dose, once daily for 7 consecutive days. On day 7, an intravenous injection of 3 microCi [14C N-methyl]erythromycin for the erythromycin breath test (EBT) was coadministered with a 2 mg oral solution of midazolam. The values for percent 14C exhaled during the first hour (for EBT) and the pharmacokinetic parameters of midazolam (AUC, Cmax, t1/2) were not affected following multiple once-daily oral doses of simvastatin 80 mg. The 95% confidence interval was 0.97 to 1.18 for EBT and 0.99 to 1.23 for midazolam AUC. In addition, the total urinary recoveries of midazolam and its 1'-hydroxy metabolites (free plus conjugate) obtained from both treatments were not statistically different (p > 0.200). These data demonstrate that multiple dosing of simvastatin, at the highest recommended clinical dose, does not significantly alter the in vivo hepatic or intestinal CYP3A4/5 activity as measured by the commonly used EBT and oral midazolam probes.
Volume
40
Issue
11
First Page
1274
Last Page
1279
ISSN
0091-2700
Published In/Presented At
Prueksaritanont, T., Vega, J. M., Rogers, J. D., Gagliano, K., Greenberg, H. E., Gillen, L., Brucker, M. J., McLoughlin, D., Wong, P. H., & Waldman, S. A. (2000). Simvastatin does not affect CYP3A activity, quantified by the erythromycin breath test and oral midazolam pharmacokinetics, in healthy male subjects. Journal of clinical pharmacology, 40(11), 1274–1279.
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
11075313
Department(s)
Administration and Leadership
Document Type
Article