Ertapenem: a Group 1 carbapenem with distinct antibacterial and pharmacological properties.
Ertapenem, a Group 1 carbapenem, is the most recent beta-lactam antibiotic to enter clinical practice in the USA and Europe. While structurally a carbapenem, the overall molecular structure of ertapenem has been modified to focus its antibacterial spectrum on important community-acquired aerobic and anaerobic pathogens, and to increase its plasma half-life, permitting once-a-day dosing for this parenteral antibiotic. A number of chemical features are responsible for the unique properties of ertapenem. The inclusion of a trans-1-hydroxyethyl group in the structure of ertapenem enables the drug to maintain antibacterial efficacy against the vast majority of beta-lactamase-producing organisms. A critical 1beta-methyl substituent shields the beta-lactam carbonyl group and serves to reduce dehydropeptidase (DHP)-1 catalysed hydrolysis of the beta-lactam, enabling ertapenem to be administered without a DHP-1 inhibitor. A meta-substituted benzoic acid substituent increases the molecular weight and lipophilicity of the molecule, and the carboxylic acid moiety, ionized at physiological pH, results in ertapenem having a net negative charge. As a result, ertapenem is highly protein bound and has an extended half-life, permitting a once-a-day treatment regimen.
Hammond
Milton L
ML
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. milton_hammond@merck.com
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D001420:Bacteria, Aerobic / Q000187:drug effects*; D001421:Bacteria, Anaerobic / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D015780:Carbapenems / Q000145:classification; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology; D000077727:Ertapenem; D006801:Humans; D007769:Lactams / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D007769:Lactams; D047090:beta-Lactams; D000077727:Ertapenem