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Assessment of the CYP3A-Mediated Drug Interaction Potential of Anacetrapib, a Potent Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Healthy Volunteers.
- Source :
-
Journal of Clinical Pharmacology . Jan2009, Vol. 49 Issue 1, p80-87. 8p. 4 Charts, 2 Graphs. - Publication Year :
- 2009
-
Abstract
- In this study, midazolam was used as a probe-sensitive CYP3A substrate to investigate the effect of anacetrapib on CYP3A activity, and ketoconazole was used as a probeinhibitor to investigate the effect of potent CYP3A inhibition on the pharmacokinetics of anacetrapib, a novel cholesteryl ester transfer protein inhibitor in development for the treatment of dyslipidemia. Two partially blinded, randomized, 2-period, fixed-sequence studies were performed. Safety, tolerability, and midazolam and anacetrapib plasma concentrations were assessed. All treatments were generally well tolerated. The geometric mean ratios (90% confidence interval) of midazolam with anacetrapib/midazolam alone for AUC[sub0-∞] and C[submax] were 1.04 (0.94, 1.14) and 1.15 (0.97, 1.37), respectively. Exposure to anacetrapib was increased by ketoconazole - specifically, the geometric mean ratios (90% confidence interval) of anacetrapib with ketoconazole/ anacetrapib alone for AUC[sub0-∞] and C[submax] were 4.58 (3.68, 5.71) and 2.37 (2.02, 2.78), respectively. The study showed that anacetrapib does not inhibit or induce CYP3A activity. Furthermore, anacetrapib appears to be a moderately sensitive substrate of CYP3A. [ABSTRACT FROM AUTHOR]
- Subjects :
- *MIDAZOLAM
*KETOCONAZOLE
*DRUG interactions
*CHEMICAL inhibitors
*PHARMACOKINETICS
Subjects
Details
- Language :
- English
- ISSN :
- 00912700
- Volume :
- 49
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 35933969
- Full Text :
- https://doi.org/10.1177/0091270008326718