Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1994 Dec;38(12):2758–2762. doi: 10.1128/aac.38.12.2758

Pharmacokinetics of the triazole antifungal agent genaconazole in healthy men after oral and intravenous administration.

P Mojaverian 1, E Radwanski 1, M B Affrime 1, M N Cayen 1, C C Lin 1
PMCID: PMC188281  PMID: 7695258

Abstract

The pharmacokinetics of genaconazole, a potent new difluorophenyl-triazole antifungal agent, was studied in 12 healthy male volunteers following a single oral or intravenous administration of the drug. In a randomized two-way crossover design, each volunteer received either two 50-mg genaconazole tablets orally or a parenteral preparation containing 100 mg of genaconazole given as a 30-min intravenous infusion. Both dosage regimens were well tolerated. Blood and urine samples were collected up to 10 days after drug administration. Concentrations of genaconazole in plasma and urine were determined by a specific high-performance liquid chromatography assay with a limit of quantitation of 0.1 microgram/ml. Pharmacokinetic evaluation following oral and intravenous doses indicated that mean values for the area under the concentration-time curve from 0 h to infinity (137 and 136 micrograms.h/ml), half-life (50 and 49 h), volume of distribution (52 and 52 liters), and clearance (12 and 12 ml/min) were independent of the route of drug administration. The oral and intravenous administrations of genaconazole yielded virtually superimposable plasma concentration-time curves, resulting in an absolute bioavailability of 100%. Amounts of unchanged genaconazole found in urine samples from 0 to 240 h after oral and intravenous doses were comparable, and urinary excretion accounted for 76 and 78% of the administered dose, respectively. Renal clearances for the two routes of administration were also similar, and renal clearance accounted for over 80% of the total body clearance. The 100% absolute bioavailability of genaconazole regardless of the route of administration provides greater dosing flexibility in various clinical settings than currently exists.

Full text

PDF
2758

Selected References

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

  1. Barriere S. L. Pharmacology and pharmacokinetics of traditional systemic antifungal agents. Pharmacotherapy. 1990;10(6 ):134S–140S. [PubMed] [Google Scholar]
  2. Clemons K. V., Hanson L. H., Perlman A. M., Stevens D. A. Efficacy of SCH39304 and fluconazole in a murine model of disseminated coccidioidomycosis. Antimicrob Agents Chemother. 1990 May;34(5):928–930. doi: 10.1128/aac.34.5.928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cook R. A., McIntyre K. A., Galgiani J. N. Effects of incubation temperature, inoculum size, and medium on agreement of macro- and microdilution broth susceptibility test results for yeasts. Antimicrob Agents Chemother. 1990 Aug;34(8):1542–1545. doi: 10.1128/aac.34.8.1542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Defaveri J., Sun S. H., Graybill J. R. Treatment of murine coccidioidal meningitis with SCH39304. Antimicrob Agents Chemother. 1990 Apr;34(4):663–664. doi: 10.1128/aac.34.4.663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dudley M. N. Clinical pharmacology of fluconazole. Pharmacotherapy. 1990;10(6 ):141S–145S. [PubMed] [Google Scholar]
  6. Kim H., Lapiguera A., Lin C. Gas chromatographic and high-performance liquid chromatographic methods for the determination of genaconazole in biological fluids. J Chromatogr B Biomed Appl. 1994 Apr 22;655(1):21–26. doi: 10.1016/0378-4347(94)00063-8. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Lee J. W., Lin C., Loebenberg D., Rubin M., Pizzo P. A., Walsh T. J. Pharmacokinetics and tissue penetration of Sch 39304 in granulocytopenic and nongranulocytopenic rabbits. Antimicrob Agents Chemother. 1989 Nov;33(11):1932–1935. doi: 10.1128/aac.33.11.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Meunier F., Lambert C., Van der Auwera P. In-vitro activity of SCH39304 in comparison with amphotericin B and fluconazole. J Antimicrob Chemother. 1990 Feb;25(2):227–236. doi: 10.1093/jac/25.2.227. [DOI] [PubMed] [Google Scholar]
  12. Perfect J. R., Wright K. A., Hobbs M. M., Durack D. T. Treatment of experimental cryptococcal meningitis and disseminated candidiasis with SCH39304. Antimicrob Agents Chemother. 1989 Oct;33(10):1735–1740. doi: 10.1128/aac.33.10.1735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Restrepo B. I., Ahrens J., Graybill J. R. Efficacy of SCH39304 in murine cryptococcosis. Antimicrob Agents Chemother. 1989 Aug;33(8):1242–1246. doi: 10.1128/aac.33.8.1242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sugar A. M., Picard M., Noble L. Treatment of murine pulmonary blastomycosis with SCH 39304, a new triazole antifungal agent. Antimicrob Agents Chemother. 1990 May;34(5):896–898. doi: 10.1128/aac.34.5.896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Tanio T., Ichise K., Nakajima T., Okuda T. In vivo efficacy of SM-8668 (Sch 39304), a new oral triazole antifungal agent. Antimicrob Agents Chemother. 1990 Jun;34(6):980–984. doi: 10.1128/aac.34.6.980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Walsh T. J., Lee J. W., Lecciones J., Kelly P., Peter J., Thomas V., Bacher J., Pizzo P. A. SCH-39304 in prevention and treatment of disseminated candidiasis in persistently granulocytopenic rabbits. Antimicrob Agents Chemother. 1990 Aug;34(8):1560–1564. doi: 10.1128/aac.34.8.1560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Walsh T. J., Lester-McCully C., Rinaldi M. G., Wallace J. E., Balis F. M., Lee J. W., Pizzo P. A., Poplack D. G. Penetration of SCH-39304, a new antifungal triazole, into cerebrospinal fluid of primates. Antimicrob Agents Chemother. 1990 Jun;34(6):1281–1284. doi: 10.1128/aac.34.6.1281. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES