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/l and 123 +/- 12 mg/l respectively. The following mean pharmacokinetic parameters were obtained after single intravenous administration: elimination half-life 10 +/- 1 h, total clearance 22 +/- 2 ml/min and volume of distribution 0.30 +/- 0.04 l/kg. After repeated administration the half-life 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 less than 0.01). Consequently, mean trough and peak steady state plasma concentrations (81 +/- 9 and 123 +/- 12 mg/l respectively) are higher than those expected from the single dose kinetics (33 +/- 4 and 76 +/- 7 mg/l respectively). This dose regimen leads to concentrations well above the MIC for most sensitive strains.(ABSTRACT TRUNCATED AT 250 WORDS)
Taburet
A M
AM
Clinical Pharmacy, Hôpital Bicêtre, Paris, France.
Guibert
J
J
Kitzis
M D
MD
Sorensen
H
H
Acar
J F
JF
Singlas
E
E
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005672:Fusidic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D013056:Spectrophotometry, Ultraviolet
D005672:Fusidic Acid