This study evaluates the hypothesis that the extent of interaction between an inhibitor (fluconazole) and an enzyme (CYP2C19) is linearly related to the plasma concentration of the inhibitor. Ten healthy subjects will be admitted to the CRC on four separate occasions. The first visit to CRC will establish the subject's baseline level of metabolic activity of CYP2C19 - the enzyme responsible for the metabolism of (S)-mephenytoin. Subjects then will be brought to steady-state concentrations of fluconazole using 20, 60 or 200 mg/day and the enzyme activity will again be measusred by giving the same test dose of 100 mg (S)-mephenytoin. In vivo inhibition constants Ki,IV will be calculated by measuring the 4'hydroxylation of (S)-mephenytoin.
Showing the most recent 10 out of 563 publications