Pharmacokinetics of Cefamandole in Patients with Normal and Impaired Renal Function

Abstract

The pharmacokinetics of cefamandole, a new cephalosporin, were investigated in 23 patients with urinary tract infections and normal or varying degrees of impairment of renal function. A daily dose of 1.5 to 3.0 g administered intramuscularly was tolerated well and resulted in very high urine concentrations. The pharmacokinetics of the antibiotic were compared with isotopically labeled [ ¹³¹ I]hippurate and [ ¹²⁵ I]iothalamate, which were used for determination of effective renal plasma flow and glomerular filtration rate, respectively. It was shown that cefamandole was excreted by glomerular filtration as well as by active tubular secretion. Probenecid inhibited the tubular secretion of cefamandole. The serum half-life of cefamandole in patients with normal renal function was approximately 1.5 h and increased in patients along with increasing impairment of renal function. Our studies indicate that a dosage regimen of 1 g of cefamandole every 8 h in patients with normal renal function results in urine concentrations sufficiently high for treatment of most common urinary tract infections. In patients with impaired renal function, the dosage interval should be increased or the dosage lowered according to the serum creatinine values.