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To investigate possible mechanisms for the long-lasting pharmacokinetic properties of cefpiramide, pharmacokinetic and renal clearance studies were carried out using rabbits. Cefazolin was employed as a reference compound. In pharmacokinetic studies, the plasma half-life (t1/2 beta) for cefpiramide was 2.7 times as long as that for cefazolin. The total body clearance (ClT) and renal clearance (ClR) for cefazolin were approximately 2.3 times larger than those for cefpiramide. In renal clearance studies, the clearance by glomerular filtration (Clf) for cefpiramide exceeded Clf for cefazolin by 2.5 times, because of lower plasma protein binding of cefpiramide. In contrast, the clearance by tubular secretion (Cls) for cefpiramide was one-fifth as small as Cls for cefazolin. The overall renal clearance (Clr) for cefazolin was 3.6 times as large as Clr for cefpiramide, being in good agreement with the cefazolin/cefpiramide ratios of ClT and ClR. Therefore, the long-lasting pharmacokinetic properties of cefpiramide was suggested to be due to the fact that cefpiramide undergoes renal tubular secretion to less extent.

Renal tubular mechanisms for excretion of cefpiramide (SM-1652) in association with its long-lasting pharmacokinetic properties.