Pharmacokinetics and bioavailability of fluconazole in patients with AIDS
| Autor: | Alan Forrest, L G Cohen, Joseph M. Scavone, P H Kazanjian, Josiah D. Rich, D DeMuria |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Adult
Male Population Administration Oral Biological Availability Pharmacology Intestinal absorption Route of administration Pharmacokinetics Oral administration medicine Humans Pharmacology (medical) education Fluconazole Acquired Immunodeficiency Syndrome education.field_of_study business.industry Crossover study Bioavailability Infectious Diseases Intestinal Absorption Female business Research Article medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 37:2187-2192 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.37.10.2187 |
| Popis: | Fluconazole pharmacokinetics were evaluated for 10 volunteers with AIDS who had no clinical evidence of gastroenteritis. Single 100-mg intravenous (i.v.) and oral (p.o.) doses were administered in a randomized, crossover design. i.v. doses were delivered by a constant-rate infusion over 30 min. Serum fluconazole concentrations were measured by gas-liquid chromatography. The i.v. and p.o. studies were modelled simultaneously by iterative two-stage analysis, which provided individual parameter estimates and a population pharmacokinetic model. Median areas under the concentration-time curves for i.v. and p.o. studies did not differ (90.6 and 99.3 micrograms/ml.h, respectively). Consistent with this finding, the median fractional bioavailability was 1.1 (range, 0.45 to 1.3), comparable to those in healthy subjects. Serum pharmacokinetics in these AIDS patients were generally similar to published data for healthy volunteers. However, following p.o. dosing, we observed a slightly delayed and highly variable time to maximum concentration in serum (median, 2 h; range, 15 min to 8 h). Data were well described by a linear, two-compartment pharmacokinetic model with first-order absorption and elimination. Repeated-measures analysis of variance found no significant differences among any of the pharmacokinetic parameters between i.v. and p.o. studies. On the basis of our findings, we suggest no change in dosage of p.o. fluconazole in patients with AIDS who show no clinical signs of enteropathy. |
| Databáze: | OpenAIRE |
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