PHARMACOKINETICS OF FUSIDIC ACID AFTER A SINGLE-DOSE OF A NEW PEDIATRIC SUSPENSION

The pharmacokinetics of fusidic acid (Fucidine(R), Leo Laboratories) w ere studied in 10 children after single oral dosing with 20 mg/kg of a new banana-flavoured paediatric suspension (titrating at 50 mg/ml). N ine 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 l evels 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 a dult volunteers with 500 mg of sodium fusidate by parenteral administr ation (infusion) then per os. The acceptability of the single dose was good. The terminal elimination half-life t1/2 (h) and the mean reside nce time (MRT, h) of fusidate were similar to those determined in heal thy adults after oral dosing, i.e. 16.0 +/- 14.5 versus 16.0 +/- 3.5 a nd 17.7 +/- 12-1 versus 17.7 +/-2.5, respectively. In contrast, the or al bioavailability of the suspension (F(approx.), %) was relatively lo w: 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. Thi s led to the calculation of an estimated total clearance (Cl(est.), ml /min) significantly less than that in the healthy adults, while the es timated apparent volume of distribution (V(d), litre/kg) was significa ntly increased (10.4 +/- 9.1 versus 21.8 +/- 2.1 and 0.73 +/- 0-53 ver sus 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 infan ts. An increased initial volume of distribution could result from less protein binding of fusidic acid. Graphic simulations show that the ad ministration of a dose of 20 mg/kg every %12 h results in effective se rum levels being obtained from the outset. A treatment schedule involv ing three doses per day (08.00, 12.00, 20.00 hours) is also theoretica lly satisfactory.