The pharmacokinetics and protein-binding of fusidic acid in patients with severe renal failure requiring either haemodialysis or continuous ambulatory peritoneal dialysis.
Fusidic acid is metabolized and excreted by the liver. It is generally assumed that renal impairment has no effect on serum concentrations. However, there are few data on the pharmacokinetics of fusidic acid in patients with chronic renal failure, particularly in those requiring dialysis. Seven patients with chronic renal failure on haemodialysis were given 500 mg sodium fusidate orally every 8 h for the 48 h between dialysis. Seven patients on continuous ambulatory peritoneal dialysis (CAPD) were given the same dosage regimen for seven doses. Fusidic acid concentrations were measured by HPLC. Accumulation was seen, and in 12 of the 14 patients steady-state pharmacokinetics had not been achieved by the third day. In haemodialysis patients, mean (range) Cmax values for the first dose were 13.0 (2.0-25.5) mg/L and for the sixth dose were 40.5 (10.1-69.9) mg/L. Serum concentrations were not reduced by haemodialysis. In CAPD patients mean Cmax values for the first dose were 16.0 (4.8-33.8) mg/L and for the seventh dose were 33.9 (23.4-61.9) mg/L. Fusidic acid concentrations of 1.0-2.3 mg/L were detected in peritoneal dialysis fluid in six of the seven CAPD patients. In both patient groups there was a tendency towards increased T(1/2) with repeated dosing. Protein-binding of fusidic acid in patient serum samples was 87.6-94.6%.
Brown
N M
NM
Department of Medical Microbiology, Southmead Health Services NHS Trust, Westbury-on-Trym, Bristol, UK.
Reeves
D S
DS
McMullin
C M
CM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005672:Fusidic Acid / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis; D011485:Protein Binding; D006435:Renal Dialysis
D000900:Anti-Bacterial Agents; D005672:Fusidic Acid