Pharmacokinetics of fusidic acid after a single dose of a new paediatric suspension

Abstract

The pharmacokinetics of fusidic acid (Fucidine, Leo Laboratories) were studied in 10 children after single oral dosing with 20 mg/kg of a new banana-flavoured paediatric suspension (titrating at 50 mg/ml). Nine blood samples were drawn from each child at 0, 1, 2, 3, 6, 8, 12, 24 and 48 h following dosing with the antibiotic. Serum fusidic acid levels were measured by high-performance liquid chromatography (HPLC). A model-independent method was used for the pharmacokinetic analysis. Results were compared with those obtained after dosing eight healthy adult volunteers with 500 mg of sodium fusidate by parenteral administration (infusion) then per os. The acceptability of the single dose was good. The terminal elimination half-life t1/2 (h) and the mean residence time (MRT, h) of fusidate were similar to those determined in healthy adults after oral dosing, i.e. 16.0 +/- 14.5 versus 16.0 +/- 3.5 and 17.7 +/- 12.1 versus 17.7 +/- 2.5, respectively. In contrast, the oral bioavailability of the suspension (Fapprox., %) was relatively low: of the order of 22.5 versus 91.0% for tablets in the healthy adult, which justifies the use of a relatively higher dose in the child. This led to the calculation of an estimated total clearance (Clest., ml/min) significantly less than that in the healthy adults, while the estimated apparent volume of distribution (Vd, litre/kg) was significantly increased (10.4 +/- 9.1 versus 21.8 +/- 2.1 and 0.73 +/- 0.53 versus 0.30 +/- 0.04, respectively). Fusidic acid is normally excreted in metabolized form (98%). The decrease in clearance could be attributed to the almost immediate saturation of liver enzymes in immature infants.(ABSTRACT TRUNCATED AT 250 WORDS)