Pharmacokinetics of cefaclor in renal failure: effects of multiple doses and hemodialysis

The pharmacokinetics of cefaclor were characterized in 15 functionally anephric patients on hemodialysis. Each patient received a 500-mg oral dose of cefaclor every 8 h for 10 days. Multiple serum drug levels were measured by bioassay on day 0 (no hemodialysis), day 10 during hemodialysis, and as single determinations 1 h after administration on days 1, 3, and 5. Analysis of cefaclor kinetics in these 15 patients along with kinetics from 24 previously studied patients showed that weight was the best single predictor of volume of distribution. The corrected creatinine clearance (calculated from serum creatinine, age, and sex) proved to be the best predictor of drug half-life (r = 0.969). Thus, a single serum creatinine test provided a better estimated of cefaclor half-life than a 24-h urine collection. Cefaclor was cleared with an average serum half-life of 2.9 h without hemodialysis and 1.5 h during hemodialysis. Cefaclor serum levels measured 1 h after administration on days 0, 1, 3, and 5 showed no evidence of accumulation. Thus, cefaclor may be administered orally in multiple doses without accumulation in functionally anephric patients. In patients on dialysis, dosage interval or quantity should be increased to compensate for doubled drug clearance dialysis.