Antibiotic activity in serum following single and repeated oral administration of sodium fusidate in volunteers.

The pharmacokinetics of antibiotic activity were investigated in 10 healthy, female volunteers receiving a single oral dose of sodium fusidate (500 mg) followed after 48 h by repeated oral dosing of 250 mg b.i.d. for 5 consecutive days. By use of turbidimetry, drug-related antibiotic activity in serum was determined and expressed as fusidic acid equivalents. After a single dose and repeated dosing, the peak concentrations were (mean +/- SE): 30 +/- 3 micrograms/ml and 27 +/- 3 micrograms/ml, respectively (NS), and the trough concentration at steady state was 8.4 +/- 1.8 micrograms/ml. The experimental and predicted accumulation ratios were 2.1 +/- 0.1 versus 1.6 +/- 0.2, respectively (P < 0.16). By use of a model independent method, the terminal elimination half-lives were estimated to be 11 +/- 1 h and 13 +/- 2 h after a single dose and repeated doses, respectively (NS). The total clearances of antibiotic activity were 2.0 +/- 0.4 l/h after a single dose and 1.6 +/- 0.2 l/h after repeated doses (P < 0.11). Model dependent pharmacokinetic parameters were also obtained by fitting a two-compartment open model to the median serum concentrations which, with respect to half-life and clearance, gave values close to those observed by use of the model independent approach. Safety-wise, biochemical parameters were within the normal range. However, a statistically significant increase in ASAT and a decrease in leucocytes were observed. The tolerability of the drug was good and only minor adverse events were reported.