Pharmacokinetic interactions of ceftazidime, imipenem and aztreonam with amikacin in healthy volunteers.
The common usage of extended spectrum beta-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 1g 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 1g 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 beta-lactam serum levels without further affecting the complete pharmacokinetic profile of each drug as obtained after administration of the drug alone.
Adamis
George
G
1st Department of Internal Medicine, Athens General Hospital "G Gennimatas", Athens, Greece.
Papaioannou
Maria G
MG
Giamarellos-Bourboulis
Evangelos J
EJ
Gargalianos
Panayotis
P
Kosmidis
John
J
Giamarellou
Helen
H
D000328:Adult; D000583:Amikacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001398:Aztreonam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D002442:Ceftazidime / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D007769:Lactams / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male
D000900:Anti-Bacterial Agents; D007769:Lactams; D015378:Imipenem; D000583:Amikacin; D002442:Ceftazidime; D001398:Aztreonam