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Antimicrob Agents Chemother. 2009 Sep;53(9):3664-74. doi: 10.1128/AAC.01448-08. Epub 2009 Jun 22.

Pharmacokinetics and buccal mucosal concentrations of a 15 milligram per kilogram of body weight total dose of liposomal amphotericin B administered as a single dose (15 mg/kg), weekly dose (7.5 mg/kg), or daily dose (1 mg/kg) in peripheral stem cell transplant patients.

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  • 1Department of Pharmacy Practice, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. gubbinspaulo@uams.edu

Abstract

The pharmacokinetics and safety of extended-interval dosing of prophylactic liposomal amphotericin B (L-AMB) in peripheral stem cell transplant recipients were evaluated. The patients received L-AMB daily at 1 mg/kg of body weight or weekly at 7.5 mg/kg or received L-AMB as a single dose (15 mg/kg). The buccal mucosal tissue concentrations of L-AMB were measured. Of the 24 patients enrolled, 5 withdrew after the initial dose due to an infusion-related reaction (n = 2) or significant increases in the serum creatinine (Scr) levels (n = 3). Weekly L-AMB dosing (7.5 mg/kg) produced mean plasma concentrations of >0.300 microg/ml for the first 7 days and >0.220 microg/ml for 7 days after the second dose. A single L-AMB dose (15 mg/kg) produced mean plasma concentrations of >0.491 microg/ml for at least 7 seven days. These concentrations are within the range of the MICs reported in the literature for susceptible strains of Candida and are at the lower limits of the MICs for Aspergillus spp. Extended-interval dosing produced buccal mucosal tissue concentrations well in excess of the MICs reported in the literature for susceptible strains of Candida and Aspergillus spp. Infusion-related reactions occurred in 24% of the patients. Baseline and end-of-study Scr, electrolyte (K+, Mg2+, PO4), and serum transaminase levels were similar across the dosage groups. Five (31%) patients met the nephrotoxicity definition prior to completion of the study. Patients in the weekly or single-dose groups experienced nephrotoxicity significantly faster than the patients in the daily dosing cohort. A weekly L-AMB dose (7.5 mg/kg) or a single L-AMB dose (15 mg/kg) produced sufficient concentrations in plasma and highly vascular tissue to warrant further studies of the safety, efficacy, and practicality of the weekly prophylactic administration of L-AMB.

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