ANTIBIOTIC-ACTIVITY IN SERUM FOLLOWING SINGLE AND REPEATED ORAL-ADMINISTRATION OF SODIUM FUSIDATE IN VOLUNTEERS

The pharmacokinetics of antibiotic activity were investigated in IO he althy, female volunteers receiving a single oral dose of sodium fusida te (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 antibi otic activity in serum was determined and expressed as fusidic acid eq uivalents. After a single dose and repeated dosing, the peak concentra tions were (mean +/- SE): 30 +/- 3 mu g/ml and 27 +/- 3 mu g/ml, respe ctively (NS), and the trough concentration at steady state was 8.4 +/- 1.8 mu g/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 m odel independent method, the terminal elimination half-lives were esti mated 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 1/h after a single dose and 1.6 +/- 0.2 1/h after re peated doses (P < O.11). Model dependent pharmacokinetic parameters we re 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 ap proach. Safety-wise, biochemical parameters were within the normal ran ge. However, a statistically significant increase in ASAT and a decrea se in leucocytes were observed. The tolerability of the drug was good and only minor adverse events were reported.