PHARMACOKINETICS OF ORAL FLUCONAZOLE WHEN USED FOR PROPHYLAXIS IN BONE-MARROW TRANSPLANT RECIPIENTS

The pharmacokinetics of fluconazole was investigated in 20 bone marrow transplant patients following oral administration of 200 mg of this d rug. Blood samples were collected from each patient at different time intervals within 48 h after the first dose, and fluconazole was measur ed in plasma by high-performance liquid chromatography with UV detecti on. Urine was collected from 14 of these patients and analyzed similar ly. The plasma concentration-time data exhibited the characteristics o f the one-compartment model with first-order absorption quite well. Th e means +/- standard deviations of half-lives for absorption and elimi nation, peak concentration, time to peak, mean residence time, apparen t volumes of distribution, area under the curve, and apparent oral cle arance observed in these patients were 2.84 +/- 1.34 h, 19.4 +/- 18.7 h, 4.45 +/- 1.86 mu g/ml, 8.34 +/- 5.97 h, 39.57 +/- 20.5 h, 0.874 +/- 0.48 liter/kg, 156.0 +/- 60.6 mu g . h/ml, and 0.0256 +/- 0.0138 lite r/h . kg, respectively. The amount of fluconazole excreted in urine in 24 h was 67.1 +/- 83 mg, which represents 33.55% +/- 41.6% of the dos e administered. Patients who developed hemorrhagic cystitis excreted s ignificantly (P less than or equal to 0.0094) more fluconazole in 24 h than did those who did not.