The effect of fluconazole on the steady-state pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine in humans.
Terfenadine is rapidly and nearly completely biotransformed during a first pass to an active acid metabolite. Accumulation of unmetabolized terfenadine has been associated with altered cardiac repolarization. Drug-drug interactions resulting in the accumulation of terfenadine have been reported for ketoconazole and erythromycin. Six subjects were given the recommended dose of terfenadine (60 mg every 12 hours) for 7 days before initiation of oral fluconazole (200 mg once daily). The mean metabolite area under the concentration-time curve increased by 34% and the time to maximum concentration of the metabolite was delayed from 2.3 to 4 hours by concurrent fluconazole. Unmetabolized terfenadine was not present in any subject, and cardiac repolarization was not significantly changed from baseline during any phase of the study. We conclude that a pharmacokinetic interaction between terfenadine and fluconazole exists; however, the absence of accumulation of parent terfenadine in plasma suggests that a clinically significant interaction is unlikely.
Honig
P K
PK
Division of Clinical Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Worham
D C
DC
Zamani
K
K
Mullin
J C
JC
Conner
D P
DP
Cantilena
L R
LR
D000328:Adult; D000368:Aged; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D015725:Fluconazole / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016593:Terfenadine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D016593:Terfenadine; D015725:Fluconazole