Pharmacokinetics of SCH-39304 in human immunodeficiency virus-infected patients following chronic oral dosing.
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.
Hardin
T C
TC
Department of Medicine, University of Texas Health Science Center, San Antonio.
Sharkey
P K
PK
Lam
Y F
YF
Wallace
J E
JE
Rinaldi
M G
MG
Graybill
J R
JR
D000284:Administration, Oral; D000328:Adult; D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002180:Candidiasis, Oral / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D014230:Triazoles / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000935:Antifungal Agents; D014230:Triazoles; C056513:Sch 39304