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Increased Gastric pH and the Bioavailability of Fluconazole and Ketoconazole

Robert A. Blum, PharmD; David T. D'Andrea; Becky M. Florentino, BA; John H. Wilton, PhD; Donald M. Hilligoss, PharmD; Mark J. Gardner, PhD; Eugenia B. Henry, PhD; Harvey Goldstein, MD; and Jerome J. Schentag, PharmD
[+] Article, Author, and Disclosure Information

Grant Support: In part by a research grant from Pfizer Central Research, Pfizer, Inc., Groton, Connecticut.

Requests for Reprints: Robert A. Blum, PharmD, The Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, 3 Gates Circle, Buffalo, NY 14209-1194.

Current Author Addresses: Drs. Blum, Wilton, and Schentag, Mr. D'Andrea, and Ms. Florentino: The Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, 3 Gates Circle, Buffalo, NY 14209-1194.

Drs. Hilligoss, Gardner, and Henry: Pfizer Central Research, Pfizer, Inc., Eastern Point Road, Groton, CT 06430.

Dr. Goldstein: Department of Medicine, Millard Fillmore Hospital, 3 Gates Circle, Buffalo, NY 14209.

Ann Intern Med. 1991;114(9):755-757. doi:10.7326/0003-4819-114-9-755
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This excerpt has been provided in the absence of an abstract.

Two orally active antifungal agents are currently available, ketoconazole and fluconazole. However, the absorption of ketoconazole depends on gastric pH for tablet disintegration and dissolution (1, 2). Reduced serum concentrations of ketoconazole have been reported in patients with achlorhydria and in patients receiving concomitant treatment with antacids or cimetidine (1-3). Our study was done to determine the effects of cimetidine-induced increases in gastric pH on the relative bioavailability of fluconazole and ketoconazole.

Methods: Twenty-four healthy male volunteers, 19 to 43 years of age, gave written informed consent to participate in the study. The study protocol was approved by the


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