Abstract
The pharmacokinetics of SCH-39304, an investigational, orally active, broad-spectrum antifungal agent, were evaluated in 17 adult, human immunodeficiency virus-positive males. Patients were studied on days 1 and 16 and were divided into the following three treatment groups: (i) patients with culture-proven oropharyngeal candidiasis who were not receiving concurrent zidovudine therapy and who were treated with 50 mg of SCH-39304 daily (n = 6); (ii) patients with culture-proven oropharyngeal candidiasis who were receiving concurrent zidovudine therapy and who were treated with 50 mg of SCH-39304 daily (n = 5); and (iii) patients with or without oropharyngeal candidiasis who were receiving concurrent zidovudine therapy and who were treated with 200 mg of SCH-39304 daily (n = 6). All patients received a single daily dose of the study medication for 16 days. Plasma samples for SCH-39304 concentration measurement were collected for 6 h following the initial dose and for 504 h following the day 16 dose. Urine was collected for 24 h following SCH-39304 administration on days 1 and 16. All samples were assayed for SCH-39304 by gas chromatography. Wide intersubject variations in SCH-39304 plasma concentration-versus-time profiles were observed on each study day. Absorption appeared to be slow, with mean day 1 peak plasma SCH-39304 concentrations of 1.2 micrograms/ml at 2.1 h (50 mg) and 3.9 micrograms/ml at 4.0 h (200 mg) after drug administration. Mean peak plasma SCH-39304 concentrations on day 16 were 7.6 micrograms/ml at 4.3 h (50 mg) and 17.2 micrograms/ml at 3.2 h (200 mg) after drug administration. Mean elimination half-lives on day 16 for the 50- and 200-mg daily dosages were 100 and 89 h, respectively. SCH-39304 was cleared primarily unchanged in the urine. Mean areas under the plasma concentration-versus-time curve (from 0 to 24 h) on day 16 reflect a lower than expected increase with the 200-mg/day regimen (314.5 microgram.h/ml) compared with that for the 50-mg/day regimen (139.9 microgram.h/ml), suggesting the potential for reduced bioavailability at higher dosages. No significant effect of concurrent zidovudine therapy on the kinetics of SCH-39304 was observed.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brammer K. W., Farrow P. R., Faulkner J. K. Pharmacokinetics and tissue penetration of fluconazole in humans. Rev Infect Dis. 1990 Mar-Apr;12 (Suppl 3):S318–S326. doi: 10.1093/clinids/12.supplement_3.s318. [DOI] [PubMed] [Google Scholar]
- Graybill J. R. New antifungal agents. Eur J Clin Microbiol Infect Dis. 1989 May;8(5):402–412. doi: 10.1007/BF01964056. [DOI] [PubMed] [Google Scholar]
- Hardin T. C., Graybill J. R., Fetchick R., Woestenborghs R., Rinaldi M. G., Kuhn J. G. Pharmacokinetics of itraconazole following oral administration to normal volunteers. Antimicrob Agents Chemother. 1988 Sep;32(9):1310–1313. doi: 10.1128/aac.32.9.1310. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huang Y. C., Colaizzi J. L., Bierman R. H., Woestenborghs R., Heykants J. Pharmacokinetics and dose proportionality of ketoconazole in normal volunteers. Antimicrob Agents Chemother. 1986 Aug;30(2):206–210. doi: 10.1128/aac.30.2.206. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kosoglou T., Perentesis G. P., Affrime M. B., Lin C. C., Mojaverian P., Radwanski E., Vlasses P. H. The effect of antacid and cimetidine on the oral absorption of the antifungal agent SCH 39304. J Clin Pharmacol. 1990 Jul;30(7):638–642. doi: 10.1002/j.1552-4604.1990.tb01867.x. [DOI] [PubMed] [Google Scholar]
- 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]
- Loebenberg D., Cacciapuoti A., Parmegiani R., Moss E. L., Jr, Menzel F., Jr, Antonacci B., Norris C., Yarosh-Tomaine T., Hare R. S., Miller G. H. In vitro and in vivo activities of SCH 42427, the active enantiomer of the antifungal agent SCH 39304. Antimicrob Agents Chemother. 1992 Feb;36(2):498–501. doi: 10.1128/aac.36.2.498. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]