Abstract
Eight healthy adults were given single oral doses of ketoconazole (200, 400, 600, and 800 mg) in the fasting state and with a standard breakfast at weekly intervals according to a balanced block design. Concentrations in serum were measured up to 32 h after the dose. Food did not reduce ketoconazole absorption or significantly alter peak ketoconazole concentrations in serum, though there was a food-related delay in achieving peak concentrations. At the 400- and 600-mg doses, food appeared to enhance absorption, but this effect was not seen at the 800-mg dose. With an increase in dose, the half-life and area under the serum concentration-time curve increased disproportionately, suggesting that the pharmacokinetics of ketoconazole may be dose dependent. Up to the 800-mg dose, the elimination of ketoconazole did not appear to be saturable. Administration of the drug with food is unlikely to be a cause of therapeutic failure.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Borelli D., Bran J. L., Fuentes J., Legendre R., Leiderman E., Levine H. B., Restrepo A., Stevens D. A. Ketoconazole, an oral antifungal: laboratory and clinical assessment of imidazole drugs. Postgrad Med J. 1979 Sep;55(647):657–661. doi: 10.1136/pgmj.55.647.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brass C., Galgiani J. N., Blaschke T. F., Defelice R., O'Reilly R. A., Stevens D. A. Disposition of ketoconazole, an oral antifungal, in humans. Antimicrob Agents Chemother. 1982 Jan;21(1):151–158. doi: 10.1128/aac.21.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Craven P. C., Graybill J. R., Jorgensen J. H., Dismukes W. E., Levine B. E. High-dose ketoconazole for treatment of fungal infections of the central nervous system. Ann Intern Med. 1983 Feb;98(2):160–167. doi: 10.7326/0003-4819-98-2-160. [DOI] [PubMed] [Google Scholar]
- Daneshmend T. K., Roberts C. J. The influence of food on the oral and intravenous pharmacokinetics of a high clearance drug: a study with labetalol. Br J Clin Pharmacol. 1982 Jul;14(1):73–78. doi: 10.1111/j.1365-2125.1982.tb04936.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Daneshmend T. K., Warnock D. W., Ene M. D., Johnson E. M., Parker G., Richardson M. D., Roberts C. J. Multiple dose pharmacokinetics of ketoconazole and their effects on antipyrine kinetics in man. J Antimicrob Chemother. 1983 Aug;12(2):185–188. doi: 10.1093/jac/12.2.185. [DOI] [PubMed] [Google Scholar]
- Daneshmend T. K., Warnock D. W., Turner A., Roberts C. J. Pharmacokinetics of ketoconazole in normal subjects. J Antimicrob Chemother. 1981 Oct;8(4):299–304. doi: 10.1093/jac/8.4.299. [DOI] [PubMed] [Google Scholar]
- Dismukes W. E., Stamm A. M., Graybill J. R., Craven P. C., Stevens D. A., Stiller R. L., Sarosi G. A., Medoff G., Gregg C. R., Gallis H. A. Treatment of systemic mycoses with ketoconazole: emphasis on toxicity and clinical response in 52 patients. National Institute of Allergy and Infectious Diseases collaborative antifungal study. Ann Intern Med. 1983 Jan;98(1):13–20. doi: 10.7326/0003-4819-98-1-13. [DOI] [PubMed] [Google Scholar]
- Hann I. M., Prentice H. G., Keaney M., Corringham R., Blacklock H. A., Fox J., Gascoigne E., Van Cutsem J. The pharmacokinetics of ketoconazole in severely immunocompromised patients. J Antimicrob Chemother. 1982 Dec;10(6):489–496. doi: 10.1093/jac/10.6.489. [DOI] [PubMed] [Google Scholar]
- Heel R. C., Brogden R. N., Carmine A., Morley P. A., Speight T. M., Avery G. S. Ketoconazole: a review of its therapeutic efficacy in superficial and systemic fungal infections. Drugs. 1982 Jan-Feb;23(1-2):1–36. doi: 10.2165/00003495-198223010-00001. [DOI] [PubMed] [Google Scholar]
- Maksymiuk A. W., Levine H. B., Bodey G. P. Pharmacokinetics of ketoconazole in patients with neoplastic diseases. Antimicrob Agents Chemother. 1982 Jul;22(1):43–46. doi: 10.1128/aac.22.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Melander A. Influence of food on the bioavailability of drugs. Clin Pharmacokinet. 1978 Sep-Oct;3(5):337–351. doi: 10.2165/00003088-197803050-00001. [DOI] [PubMed] [Google Scholar]
- Männistö P. T., Mäntylä R., Nykänen S., Lamminsivu U., Ottoila P. Impairing effect of food on ketoconazole absorption. Antimicrob Agents Chemother. 1982 May;21(5):730–733. doi: 10.1128/aac.21.5.730. [DOI] [PMC free article] [PubMed] [Google Scholar]