We performed a prospective evaluation of pharmacokinetics of
fluconazole administered for prophylactic purposes to 19 patients after cytotoxic
chemotherapy for
hematological malignancies. On days 7 and 15, we obtained 5 ml of blood from each patient. If
fluconazole was administered orally, blood samples were drawn 2, 8, and 24 hr after ingestion of the
drug. If it was administered intravenously, blood samples were drawn 1, 8, and 24 hr post-injection. Serum
fluconazole levels were analyzed by HPLC with ultraviolet light detection. In patients receiving 200 or 400 mg of
fluconazole per day, maximal serum levels were 7.9 and 15.6 mg/l and minimum levels were 5.0 and 10.3 mg/l, respectively. There was no significant difference in serum
fluconazole levels comparing the levels after oral and
intravenous administration, and pharmacokinetic parameters of
fluconazole were comparable at each time point within one dose level. However, considerable variation in serum
fluconazole levels was noted in this study, as the maximal serum levels ranged from 4.0 to 13.3 mg/l and from 8.7 to 26.9 mg/l in patients receiving 200 and 400 mg of
fluconazole orally, respectively. These variations may be associated with prophylactic failures for patients with insufficient
fluconazole concentrations. Multiple regression analysis showed significant correlation between serum
fluconazole levels and some variables including dose of
fluconazole, age, serum
aspartate aminotransferase levels and blood
urea nitrogen levels. These variations may be associated with disturbance of body water balance, such as massive
hemorrhage and
dehydration.