Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1995 Aug;39(8):1671–1675. doi: 10.1128/aac.39.8.1671

Effects of an acidic beverage (Coca-Cola) on absorption of ketoconazole.

T W Chin 1, M Loeb 1, I W Fong 1
PMCID: PMC162805  PMID: 7486898

Abstract

Absorption of ketoconazole is impaired in patients with achlorhydria. The purpose of this study was to determine the effectiveness of a palatable acidic beverage (Coca-Cola Classic, pH 2.5) in improving the absorption of ketoconazole in the presence of drug-induced achlorhydria. A prospective, randomized, three-way crossover design with a 1-week wash-out period between each treatment was employed. Nine healthy nonsmoking, nonobese volunteers between 22 and 41 years old were studied. Each subject was randomized to receive three treatments: (A) ketoconazole 200-mg tablet with water (control), (B) omeprazole (60 mg) followed by ketoconazole (200 mg) taken with water, and (C) omeprazole (60 mg) followed by ketoconazole (200 mg) taken with 240 ml of Coca-Cola Classic. The pH values of gastric aspirates were checked after omeprazole was administered to confirm attainment of a pH of > 6. Multiple serum samples were obtained for measurements of ketoconazole concentrations by high-pressure liquid chromatography. The mean area under the ketoconazole concentration-time curve from zero to infinity for the control treatment (17.9 +/- 13.1 mg.h/liter) was significantly greater than that for treatment B (3.5 +/- 5.1 mg.h/liter; 16.6% +/- 15.0% of control). The mean peak concentration was highest for the control treatment (4.1 +/- 1.9 micrograms/ml), for which the mean peak concentration showed a significant increase over that for treatment B. The absorption of ketoconazole was reduced in the presence of omeprazole-induced achlorhydria. However, drug absorption was significantly increased, to approximately 65% of the mean for the control treatment, when the drug was taken with an acidic beverage, such as Coca-Cola.

Full Text

The Full Text of this article is available as a PDF (230.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blum R. A., D'Andrea D. T., Florentino B. M., Wilton J. H., Hilligoss D. M., Gardner M. J., Henry E. B., Goldstein H., Schentag J. J. Increased gastric pH and the bioavailability of fluconazole and ketoconazole. Ann Intern Med. 1991 May 1;114(9):755–757. doi: 10.7326/0003-4819-114-9-755. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Carlson J. A., Mann H. J., Canafax D. M. Effect of pH on disintegration and dissolution of ketoconazole tablets. Am J Hosp Pharm. 1983 Aug;40(8):1334–1336. [PubMed] [Google Scholar]
  4. Carver P. L., Berardi R. R., Knapp M. J., Rider J. M., Kauffman C. A., Bradley S. F., Atassi M. In vivo interaction of ketoconazole and sucralfate in healthy volunteers. Antimicrob Agents Chemother. 1994 Feb;38(2):326–329. doi: 10.1128/aac.38.2.326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Como J. A., Dismukes W. E. Oral azole drugs as systemic antifungal therapy. N Engl J Med. 1994 Jan 27;330(4):263–272. doi: 10.1056/NEJM199401273300407. [DOI] [PubMed] [Google Scholar]
  6. Daneshmend T. K., Warnock D. W. Clinical pharmacokinetics of ketoconazole. Clin Pharmacokinet. 1988 Jan;14(1):13–34. doi: 10.2165/00003088-198814010-00002. [DOI] [PubMed] [Google Scholar]
  7. Diletti E., Hauschke D., Steinijans V. W. Sample size determination for bioequivalence assessment by means of confidence intervals. Int J Clin Pharmacol Ther Toxicol. 1991 Jan;29(1):1–8. [PubMed] [Google Scholar]
  8. Fan-Havard P., Capano D., Smith S. M., Mangia A., Eng R. H. Development of resistance in candida isolates from patients receiving prolonged antifungal therapy. Antimicrob Agents Chemother. 1991 Nov;35(11):2302–2305. doi: 10.1128/aac.35.11.2302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goff D. A., Koletar S. L., Buesching W. J., Barnishan J., Fass R. J. Isolation of fluconazole-resistant Candida albicans from human immunodeficiency virus-negative patients never treated with azoles. Clin Infect Dis. 1995 Jan;20(1):77–83. doi: 10.1093/clinids/20.1.77. [DOI] [PubMed] [Google Scholar]
  10. Howden C. W., Forrest J. A., Reid J. L. Effects of single and repeated doses of omeprazole on gastric acid and pepsin secretion in man. Gut. 1984 Jul;25(7):707–710. doi: 10.1136/gut.25.7.707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lake-Bakaar G., Quadros E., Beidas S., Elsakr M., Tom W., Wilson D. E., Dincsoy H. P., Cohen P., Straus E. W. Gastric secretory failure in patients with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1988 Sep 15;109(6):502–504. doi: 10.7326/0003-4819-109-6-502. [DOI] [PubMed] [Google Scholar]
  12. Lake-Bakaar G., Tom W., Lake-Bakaar D., Gupta N., Beidas S., Elsakr M., Straus E. Gastropathy and ketoconazole malabsorption in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1988 Sep 15;109(6):471–473. doi: 10.7326/0003-4819-109-6-471. [DOI] [PubMed] [Google Scholar]
  13. Lelawongs P., Barone J. A., Colaizzi J. L., Hsuan A. T., Mechlinski W., Legendre R., Guarnieri J. Effect of food and gastric acidity on absorption of orally administered ketoconazole. Clin Pharm. 1988 Mar;7(3):228–235. [PubMed] [Google Scholar]
  14. Lind T., Cederberg C., Ekenved G., Haglund U., Olbe L. Effect of omeprazole--a gastric proton pump inhibitor--on pentagastrin stimulated acid secretion in man. Gut. 1983 Apr;24(4):270–276. doi: 10.1136/gut.24.4.270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Piscitelli S. C., Goss T. F., Wilton J. H., D'Andrea D. T., Goldstein H., Schentag J. J. Effects of ranitidine and sucralfate on ketoconazole bioavailability. Antimicrob Agents Chemother. 1991 Sep;35(9):1765–1771. doi: 10.1128/aac.35.9.1765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rex J. H., Rinaldi M. G., Pfaller M. A. Resistance of Candida species to fluconazole. Antimicrob Agents Chemother. 1995 Jan;39(1):1–8. doi: 10.1128/aac.39.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Tavitian A., Raufman J. P., Rosenthal L. E., Weber J., Webber C. A., Dincsoy H. P. Ketoconazole-resistant Candida esophagitis in patients with acquired immunodeficiency syndrome. Gastroenterology. 1986 Feb;90(2):443–445. doi: 10.1016/0016-5085(86)90946-7. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES