Determination of cefalexin pharmacokinetics and dosage adjustments in relation to renal function

Following oral administration of a single 500-mg dose of cefalexin, serum and urine levels of the antibiotic were determined comparatively in ten normal subjects, ten patients with renal impairment, and ten patients with chronic nephritis on maintenance hemodialysis. In normal subjects, mean serum peak levels (12.0 +/- 0.8 mcg/ml) were observed 2 hours after drug administration. Absorption half-time (Ta1/2) averaged 0.82 hour and mean serum half-life (T 1/2) was 1.03 hours. Urinary recovery of cefalexin over a 6-hour period amounted to 64 per cent of the ingested dose. The renal clearance of the drug was 214 ml/min. In patients with renal impairment and in patients on maintenance hemodialysis, total elimination rate constant (Ke) was markedly lower (CrCl=0; Ke=Km=0.0766), whereas serum half-life (T 1/2) was significantly increased, reaching theoretically 8.47 hours in patinets with creatinine clearance of 0 ml/min. A correlation was established between Ke values and the creatinine clearances of the patients under study (Ke=0.0766 + 0.0060 CrCl). Initial loading doses, maintenance doses, and intervals adjusted to creatinine clearances were calculated from these data; accurate dosage schedules well adjusted to the renal status of each individual patient were derived from the calculated values.