期刊
CLINICAL PHARMACOLOGY & THERAPEUTICS
卷 85, 期 1, 页码 78-85出版社
WILEY
DOI: 10.1038/clpt.2008.186
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资金
- National Center for Research Resources [5 M01 RR-00079]
- US Public Health Service
- National Institutes of Health [T32 GM07546]
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000079] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007546] Funding Source: NIH RePORTER
The effects of single doses of intravenous (IV) ciprofloxacin and rifampin and of multiple doses of rifampin on glyburide exposure and blood glucose levels were investigated in nine healthy volunteers. A single IV dose of rifampin significantly increased the area under the concentration-time curve (AUC) of glyburide and its metabolite. Blood glucose levels were significantly lower than those observed after dosing with glyburide alone. Multiple doses of rifampin induced an increase in liver enzyme levels, leading to a marked decrease in glyburide exposure and blood glucose levels. When IV rifampin was administered after multiple doses of rifampin, the inhibition of hepatic uptake transporters masked the induction effect; however, the relative changes in AUC for glyburide and its hydroxyl metabolite were similar to those seen under noninduced conditions. The studies reported here demonstrate how measurements of the levels of both the parent drug and its primary metabolite are useful in unmasking simultaneous drug-drug induction and inhibition effects and in characterizing enzymatic vs. transporter mechanisms.
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