Abstract
Single oral doses of ketoconazole (200 mg) or miconazole (250 mg) were given in a randomized cross-over study to 10 healthy volunteers. Ketoconazole with administered (i) after fasting (both brand 1 [Orion Pharmaceutical Co.] and brand 2 [Janssen Pharmaceutica] were tested), (ii) after a standardized meal (660 kilocalories; 2,772 kJ) (brand 1), and (iii) with 300 ml of orange juice (pH 3.8) (brand 1). Miconazole was administered after fasting. Venous blood samples for high-performance liquid chromatography determinations of ketoconazole and gas chromatographic analyses of miconazole were drawn periodically up to 24 h. The concentrations of ketoconazole in sera attained with the two brands were not statistically different. The peak concentrations of ketoconazole attained with brand 1 were 4.1 +/- 0.3 micrograms/ml (mean +/- standard error of the mean) after fasting, 2.3 +/- 0.3 micrograms/ml after the standardized meal (P less than 0.01), and 3.6 +/- 0.2 micrograms/ml with orange juice. The peak concentrations were reached in 1.4, 2.3 (P less than 0.05), and 1.8 h, respectively, whereas the areas under the serum concentration-time curves were 14.4 +/- 2.21, 8.6 +/- 1.33 (P less than 0.05), and 13.4 +/- 1.30 micrograms.h/ml, respectively. The half-lives (1.7 to 2 h) did not vary significantly among the different regimens. Compared with ketoconazole, oral absorption of miconazole was poor (peak concentration, 0.47 +/- 0.7 micrograms/ml; time to reach the peak concentration, 2.6 h; area under the serum concentration-time curve, 1.10 +/- 0.20 micrograms.h/ml).
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Selected References
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- Alton K. B. Determination of the antifungal agent, ketoconazole, in human plasma by high-performance liquid chromatography. J Chromatogr. 1980 Dec 12;221(2):337–344. doi: 10.1016/s0378-4347(00)84319-4. [DOI] [PubMed] [Google Scholar]
- Odds F. C. Laboratory evaluation of antifungal agents: a comparative study of five imidazole derivatives of clinical importance. J Antimicrob Chemother. 1980 Nov;6(6):749–761. doi: 10.1093/jac/6.6.749. [DOI] [PubMed] [Google Scholar]
- Van Der Meer J. W., Keuning J. J., Scheijgrond H. W., Heykants J., Van Cutsem J., Brugmans J. The influence of gastric acidity on the bio-availability of ketoconazole. J Antimicrob Chemother. 1980 Jul;6(4):552–554. doi: 10.1093/jac/6.4.552. [DOI] [PubMed] [Google Scholar]
- Welling P. G. Influence of food and diet on gastrointestinal drug absorption: a review. J Pharmacokinet Biopharm. 1977 Aug;5(4):291–334. doi: 10.1007/BF01061694. [DOI] [PubMed] [Google Scholar]