The effect of fluconazole on the steady‐state pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine in humans

Peter K. Honig, Dale Wortham, Kaveh Zamani, James C. Mullin, Dale P. Conner, Louis R. Cantilena

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

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. Clinical Pharmacology and Therapeutics (1993) 53, 630–636; doi:

Original languageEnglish (US)
Pages (from-to)630-636
Number of pages7
JournalClinical Pharmacology and Therapeutics
Volume53
Issue number6
DOIs
StatePublished - 1993
Externally publishedYes

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Terfenadine
Fluconazole
Pharmacokinetics
Ketoconazole
Clinical Pharmacology
Erythromycin
Area Under Curve
Acids

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

The effect of fluconazole on the steady‐state pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine in humans. / Honig, Peter K.; Wortham, Dale; Zamani, Kaveh; Mullin, James C.; Conner, Dale P.; Cantilena, Louis R.

In: Clinical Pharmacology and Therapeutics, Vol. 53, No. 6, 1993, p. 630-636.

Research output: Contribution to journalArticle

Honig, Peter K. ; Wortham, Dale ; Zamani, Kaveh ; Mullin, James C. ; Conner, Dale P. ; Cantilena, Louis R. / The effect of fluconazole on the steady‐state pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine in humans. In: Clinical Pharmacology and Therapeutics. 1993 ; Vol. 53, No. 6. pp. 630-636.
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N2 - 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. Clinical Pharmacology and Therapeutics (1993) 53, 630–636; doi:

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