PHARMACOKINETICS OF SODIUM FUSIDATE AFTER SINGLE AND REPEATED INFUSIONS AND ORAL-ADMINISTRATION OF A NEW FORMULATION

The pharmacokinetics of sodium fusidate were studied in eight healthy volunteers (five males and three females) aged 21 to 33 years (29.1 ± 1.5), weight 46 to 79 kg (61.6 ±4.0 kg). First, the subjects were given 500 mg of sodium fusidate by infusion over two hours; secondly, one month later, the volunteers were given 500 mg of fusidate by infusion every eight hours for three days; thirdly, two 250 mg tablets of a new film coated formulation were administered as a single dose. Plasma concentrations of fusidate were measured by HPLC. Peak plasma concentrations reached at the end of the first and the last infusions were 52±5 mg/1 and 123± 12 mg/1 respectively. The following mean pharmacokinetic parameters were obtained after single intravenous administration: elimination half-life 10±l h, total clearance 22±2ml/min and volume of distribution 0.30 ±0.04 I/kg. After repeated administration the halflife and the volume of distribution remained unchanged whereas total clearance was halved (11 ± 1 ml/min). This leads to an experimental accumulation ratio (3.6 ±0.2) higher than the theoretical one (1.8 ±0.1; P<0.01). Consequently, mean trough and peak steady state plasma concentrations (81 ±9 and 123 ± 12 mg/1 respectively) are higher than those expected from the single dose kinetics (33 ±4 and 76 ±7 mg/1 respectively). This dose regimen leads to concentrations well above the MIC for most sensitive strains. After oral administration Cmax was 33 ±3 mg/1, obtained 2.1 ±0.3 h after drug intake; the mean half-life (16±3h) was not statistically different from that measured after intravenous injection. The mean absolute bioavailability was 91 ±5% (range 70–118%). © 1990 The British Society for Antimicrobial Chemotherapy.