Serum levels of fluconazole in patients after cytotoxic chemotherapy for hematological malignancy.
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.
Kami
M
M
Department of Hematology and Oncology, Faculty of Medicine, The University of Tokyo, Japan. kami-tky@umin.ac.jp
Sawada
Y
Y
Mori
S
S
Hirate
J
J
Kojima
N
N
Kanda
Y
Y
Moriya
A
A
Yuji
K
K
Saito
T
T
Chiba
S
S
Hirai
H
H
D000328:Adult; D000367:Age Factors; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001219:Aspartate Aminotransferases / Q000097:blood; D004305:Dose-Response Relationship, Drug; D015725:Fluconazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019337:Hematologic Neoplasms / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D011446:Prospective Studies; D012044:Regression Analysis; D014508:Urea / Q000097:blood
D000935:Antifungal Agents; D000970:Antineoplastic Agents; D015725:Fluconazole; D014508:Urea; D001219:Aspartate Aminotransferases