Pharmacokinetic interactions of ceftazidime, imipenem and aztreonam with amikacin in healthy volunteers

Abstract

The common usage of extended spectrum β-lactams co-administered with amikacin in everyday clinical practice for infections by multidrug-resistant isolates has created the need to search for pharmacokinetic interaction. Eighteen healthy volunteers were enrolled in the study; six were administered 1 g of ceftazidime singly intravenously or combined with 0.5 g of amikacin; six received 0.5 g of imipenem singly or combined with 0.5 g of amikacin and six 1 g of aztreonam singly or combined with 0.5 g of amikacin. Blood and urine samples were collected at regular time intervals and apparent serum levels were determined by a microbiological assay. Co-administration of ceftazidime and amikacin resulted in higher C max and AUC for amikacin than when administered alone. Co-administration of imipenem and amikacin resulted in higher C max for imipenem than when administered alone. The tested interactions did not affect plasma half-life ( t 1/2) and clearance rate of any antimicrobial compared with its single administration. All tested drugs were mainly eliminated by glomerular filtration. It is concluded that co-administration of ceftazidime, imipenem or aztreonam with amikacin in healthy volunteers might affect C max and AUC without influencing any other pharmacokinetic parameter. The probable clinical endpoint is that giving ceftazidime, imipenem or aztreonam with amikacin might result in a transient elevation of β-lactam serum levels without further affecting the complete pharmacokinetic profile of each drug as obtained after administration of the drug alone.