title: Effective fluconazole therapy for liver transplant recipients during continuous hemodiafiltration.
abstract: Fungal infections are still one of the main causes of death and complications after solid organ and bone marrow transplants. The authors evaluated the effect of continuous hemodiafiltration (CHDF) on the pharmacokinetics of fluconazole in liver transplant recipients. Six liver transplant patients (primary biliary cirrhosis, n = 2; fulminant hepatitis, n = 2; viral hepatitis, n = 2) were enrolled in this study. In one patient not receiving CHDF, the fluconazole levels increased with increasing dosages. In contrast, in patients undergoing CHDF, the dosage of fluconazole was increased from 100 mg/d to 200 mg/d, but fluconazole did not reach the targeted levels. It appears that the targeted trough level cannot be achieved by administration of fluconazole at a dosage of 100 to 200 mg/d during CHDF. A higher dosage (600-1000 mg/d) of fluconazole may be required to achieve the therapeutic drug level in patients undergoing CHDF. In patients undergoing CHDF, fluconazole was given at a dosage of 800 mg/d and reached the targeted levels. In addition, after CHDF, the dosage of fluconazole was decreased to 100 mg/d, and fluconazole reached the near-targeted trough level. These results demonstrate that CHDF removes fluconazole from the blood at an efficiently high rate, resulting in its ineffective blood level. To guarantee safe and effective fluconazole therapy, the trough levels should be monitored routinely during CHDF.
authors.affiliation: Department of Pharmacy, Hokkaido University Hospital, Hokkaido University, Sapporo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kishino
authors.forename: Y
authors.initials: Y
authors.lastname: Koshinami
authors.forename: T
authors.initials: T
authors.lastname: Hosoi
authors.forename: N
authors.initials: N
authors.lastname: Suda
authors.forename: Y
authors.initials: Y
authors.lastname: Takekuma
authors.forename: S
authors.initials: S
authors.lastname: Gandoh
authors.forename: H
authors.initials: H
authors.lastname: Furukawa
authors.forename: S
authors.initials: S
authors.lastname: Todo
authors.forename: K
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D000328:Adult; D000465:Algorithms; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006440:Hemofiltration; D006801:Humans; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole