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. 1994 Jan;38(1):90–95. doi: 10.1128/aac.38.1.90

In vivo pharmacokinetics and pharmacodynamics of topical ketoconazole and miconazole in human stratum corneum.

L K Pershing 1, J Corlett 1, C Jorgensen 1
PMCID: PMC284402  PMID: 8141586

Abstract

A direct study evaluating whether differential drug uptake of topical 2% miconazole and 2% ketoconazole from cream formulations into human stratum corneum correlated with differential pharmacological activity against Candida albicans was investigated in healthy human subjects. A single 24-h topical dose of 2% ketoconazole cream or 2% miconazole cream was applied unoccluded, at the same dose (2.6 mg of formulation per cm2 of surface area), at four skin sites on both ventral forearms of six human subjects. At the end of the treatment, residual drug was removed with a tissue from all sites and the treated site was tape stripped 11 times, either 1, 4, 8, or 24 h later. The first tape disc was discarded. The remaining tape discs, 2 through 11, were combined and extracted for drug quantification by high-performance liquid chromatography and bioactivity against C. albicans growth in vitro. Topical 2% ketoconazole produced 14-, 10-, and 7-fold greater drug concentrations in stratum corneum than 2% miconazole at 1, 4, and 8 h after a single topical dose. Ketoconazole and miconazole concentrations in the stratum corneum were similar 24 h after drug removal. Tape disc extracts from 2% ketoconazole-treated skin sites demonstrated significantly greater bioactivity in the bioassay than 2% miconazole. The increased efficacy of 2% ketoconazole compared with that of 2% miconazole in vitro reflects their differential uptake into the stratum corneum and inherent pharmacological activity. Tape stripping the drug-treated site in conjunction with a bioassay is therefore a useful approach in the determination of bioavailability of topical antifungal agents.

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Selected References

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  1. Borgers M., Van den Bossche H., De Brabander M. The mechanism of action of the new antimycotic ketoconazole. Am J Med. 1983 Jan 24;74(1B):2–8. doi: 10.1016/0002-9343(83)90507-7. [DOI] [PubMed] [Google Scholar]
  2. Brass C., Shainhouse J. Z., Stevens D. A. Variability of agar dilution-replicator method of yeast susceptibility testing. Antimicrob Agents Chemother. 1979 Jun;15(6):763–768. doi: 10.1128/aac.15.6.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brugmans J. P., Van Cutsem J. M., Thienpont D. C. Treatment of long-term tinea pedis with miconazole. Double-blind clinical evaluation. Arch Dermatol. 1970 Oct;102(4):428–432. [PubMed] [Google Scholar]
  4. Cohen J. Antifungal chemotherapy. Lancet. 1982 Sep 4;2(8297):532–537. doi: 10.1016/s0140-6736(82)90610-9. [DOI] [PubMed] [Google Scholar]
  5. D'Mello A. P., D'Souza M. J., Bates T. R. Pharmacokinetics of ketoconazole-antipyrine interaction. Lancet. 1985 Jul 27;2(8448):209–210. doi: 10.1016/s0140-6736(85)91517-x. [DOI] [PubMed] [Google Scholar]
  6. Dieperink H., Kemp E., Leyssac P. P., Starklint H., Wanscher M., Nielsen J., Jørgensen K. A., Faber V., Flachs H. Ketoconazole and cyclosporine A: combined effects on rat renal function and on serum and tissue cyclosporine A concentration. Clin Nephrol. 1986;25 (Suppl 1):S137–S143. [PubMed] [Google Scholar]
  7. Dieperink H., Møller J. Ketoconazole and cyclosporin. Lancet. 1982 Nov 27;2(8309):1217–1217. doi: 10.1016/s0140-6736(82)91231-4. [DOI] [PubMed] [Google Scholar]
  8. Dixon D., Shadomy S., Shadomy H. J., Espinel-Ingroff A., Kerkering T. M. Comparison of the in vitro antifungal activities of miconazole and a new imidazole, R41,400. J Infect Dis. 1978 Aug;138(2):245–248. doi: 10.1093/infdis/138.2.245. [DOI] [PubMed] [Google Scholar]
  9. Engelhard D., Stutman H. R., Marks M. I. Interaction of ketoconazole with rifampin and isoniazid. N Engl J Med. 1984 Dec 27;311(26):1681–1683. doi: 10.1056/NEJM198412273112606. [DOI] [PubMed] [Google Scholar]
  10. Galgiani J. N., Stevens D. A. Antimicrobial susceptibility testing of yeasts: a turbidimetric technique independent of inoculum size. Antimicrob Agents Chemother. 1976 Oct;10(4):721–728. doi: 10.1128/aac.10.4.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Glynn A. M., Slaughter R. L., Brass C., D'Ambrosio R., Jusko W. J. Effects of ketoconazole on methylprednisolone pharmacokinetics and cortisol secretion. Clin Pharmacol Ther. 1986 Jun;39(6):654–659. doi: 10.1038/clpt.1986.114. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Henry H. L. Effect of ketoconazole and miconazole on 25-hydroxyvitamin D3 metabolism by cultured chick kidney cells. J Steroid Biochem. 1985 Dec;23(6A):991–994. doi: 10.1016/0022-4731(85)90057-3. [DOI] [PubMed] [Google Scholar]
  14. Lefler E., Stevens D. A. Inhibition and killing of Candida albicans in vitro by five imidazoles in clinical use. Antimicrob Agents Chemother. 1984 Apr;25(4):450–454. doi: 10.1128/aac.25.4.450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Long E. Warfarin-miconazole interaction. Arch Intern Med. 1983 Nov;143(11):2214–2215. [PubMed] [Google Scholar]
  16. McIntyre K. A., Galgiani J. N. In vitro susceptibilities of yeasts to a new antifungal triazole, SCH 39304: effects of test conditions and relation to in vivo efficacy. Antimicrob Agents Chemother. 1989 Jul;33(7):1095–1100. doi: 10.1128/aac.33.7.1095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Pershing L. K., Silver B. S., Krueger G. G., Shah V. P., Skelley J. P. Feasibility of measuring the bioavailability of topical betamethasone dipropionate in commercial formulations using drug content in skin and a skin blanching bioassay. Pharm Res. 1992 Jan;9(1):45–51. doi: 10.1023/a:1018975626210. [DOI] [PubMed] [Google Scholar]
  19. Rolan P. E., Somogyi A. A., Drew M. J., Cobain W. G., South D., Bochner F. Phenytoin intoxication during treatment with parenteral miconazole. Br Med J (Clin Res Ed) 1983 Dec 10;287(6407):1760–1760. doi: 10.1136/bmj.287.6407.1760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sud I. J., Feingold D. S. Mechanisms of action of the antimycotic imidazoles. J Invest Dermatol. 1981 Jun;76(6):438–441. doi: 10.1111/1523-1747.ep12521036. [DOI] [PubMed] [Google Scholar]
  21. Testa B., Jenner P. Inhibitors of Cytochrome P-450s and their mechanism of action. Drug Metab Rev. 1981;12(1):1–117. doi: 10.3109/03602538109011082. [DOI] [PubMed] [Google Scholar]

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