IngentaConnect Optimal prophylactic dosage and disposition of micafungin in livi...

Abstract:

Kishino S, Ohno K, Shimanura T, Furukawa H, Todo S. Optimal prophylactic dosage and disposition of micafungin in living donor liver recipients.

Clin Transplant 2004 DOI: 10.1111/j.1399-0012.2004.00272.x

Micafungin, a new candin antifungal drug, has a good safety profile and a significant therapeutic effect against Candida and Aspergillus. Little is known, however, about the optimal prophylactic dosage and the disposition of micafungin in liver transplant recipients, or about the effect of continuous venovenous hemodialysis (CVVH) on the pharmacokinetics of micafungin. Six living donor liver transplant patients were enrolled in this study. The mean C_max and C_min (trough) values of micafungin in plasma were 6.31 ± 1.08 and 1.65 ± 0.54 μg/mL, respectively. The mean elimination half-life (t_1/2) and mean area under the curve up to 12 h post-dosing (AUC 0-12 h) were 13.63 ± 2.77 h and 50.04 ± 6.48 μg·h/mL, respectively. The concentrations of micafungin at the inlet and outlet of the dialyzer were very similar. The mean (±SD) ratio of micafungin concentrations at the inlet and outlet of the dialyzer (coutlet/cinlet) and the clearance of micafungin were 0.96 ± 0.04 and 0.054 ± 0.04 mL/min/kg, respectively. The amount in the ultrafiltrate was 1.0 mg. Micafungin effectively prevents systemic fungal infection in patients who have undergone liver transplantation. No significant differences were observed in the disposition of micafungin in recipients, and the therapeutic drug level can be achieved by administration of micafungin at a dosage of 40-50 mg/d. The CVVH had little effect on micafungin kinetics, and no dose adjustment or modification of dosing interval was needed during CVVH.

Keywords: continuous venovenous hemodialysis; liver transplantation; micafungin; optimal prophylactic dosage; pharmacokinetics

Document Type: Research article

DOI: 10.1111/j.1399-0012.2004.00272.x

Affiliations: 1: Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, Tokyo 2: First Department of Surgery, Hokkaido University Hospital, School of Medicine, Hokkaido University, Sapporo, Japan

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