Overview of a new carbapenem, panipenem/betamipron.
Carbapenems are beta-lactam antibiotics with a broad antibacterial spectrum and a potent bactericidal activity against both aerobic and anaerobic Gram-positive and Gram-negative organisms. They have been widely investigated in the past, and imipenem/cilastatin (IPM/CS), panipenem/betamipron (PAPM/BP), meropenem (MEPM) and biapenem (BIPM) are presently in clinical use or under trial. Of the carbapenems, imipenem is not readily hydrolysed by microbial beta-lactamase but is hydrolysed to open the beta-lactam ring by DHP-I from kidney and other tissues. In order to achieve greater stability to the enzyme and to prolong the action of the carbapenem in vivo, the co-administration of CS with IPM or the attainment of the chemical construction of the 1-beta methylcarbapenem derivatives in the case of MEPM and BIPM have been performed. However, some difference was found in the DHP-I activity with these carbapenems, but there was no significant difference in the pharmacokinetic parameters: AUC, CLtot, t1/2 and MRT except urinary clearance after administration of these compounds to humans. Considering that MRT as the amount of the antibiotics retained in the body is a clinically important parameter, the structural susceptibility of the carbapenems to the decomposition by DHP-I was suggested to have no clinically meaningful correlation with the pharmacokinetics of these compounds.
Shimada
J
J
Division of Clinical Pharmacology, St. Marianna University School of Medicine, Kawasaki, Japan.
Kawahara
Y
Y
D000409:Alanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D015780:Carbapenems / Q000493:pharmacokinetics* / Q000494:pharmacology; D004285:Dogs; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D008252:Macaca fascicularis; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013845:Thienamycins / Q000493:pharmacokinetics* / Q000494:pharmacology
D015780:Carbapenems; D013845:Thienamycins; C047207:N-benzoylalanine; D000409:Alanine; C039536:panipenem