RiteMED Meropenem Trihydrate Mechanism of Action

Pharmacology: Pharmacodynamics: Meropenem is a synthetic carbapenem beta-lactam antibiotic that is structurally related to imipenem. It is more stable to renal dehydropeptidase 1 (DHP 1) than imipenem and therefore does not require concomitant administration with a DHP 1 inhibitor such as cilastatin. It has a broad spectrum antibacterial activity. Meropenem is active against Gram-positive, Gram-negative and some anaerobic bacteria. It readily penetrates the bacterial cells and interferes with the synthesis of the peptidoglycan layer, an important structure of the cell wall, which leads to cell death. Meropenem is highly resistant to hydrolysis by a variety of beta-lactamases (including penicillinases, cephalosporinases and extended-spectrum beta-lactamases).
Antimicrobial spectrum of activity: Meropenem is active against most strains of the following microorganisms both in vitro and in clinical infections: (See Table 1.)

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Meropenem is active in vitro against the following microorganisms; however clinical significance is unknown: (See Table 2.)

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It is suggested to carry out susceptibility tests.
Pharmacokinetics: Intravenous (IV) bolus injection of single dose meropenem 500 mg or 1 g over 5 minutes in normal adults results in peak plasma concentrations (C_max) of about 50 and 112 mcg/mL, respectively. The same doses infused over a period of 30 minutes produce C_max of 23 and 49 mcg/mL respectively.
Meropenem is distributed into a wide range of body fluids and tissues, including bronchial mucosa, lungs, bile, gynecologic tissue (endometrium, myometrium, ovary, cervix, fallopian tube), muscle, heart valves, skin, interstitial and peritoneal fluids, and cerebrospinal fluid.
Approximately 70% of the IV dose is eliminated in urine as unchanged drug by tubular secretion and glomerular filtration. A further 28% is recovered as the microbiologically inactive metabolite. Plasma protein binding is approximately 2%. Urinary concentration in excess of 10 mcg/mL is maintained for up to 5 hours after a 500 mg dose. No accumulation of meropenem in plasma or urine was observed after 500 mg and 1 g doses administered every 8 and 6 hours, respectively, in adults with normal renal function.
The plasma half-life (t_½) of meropenem is approximately 1 hour in adults with normal renal function and 1.5 hours in children 3 months to 2 years old. Plasma t_½ is increased and clearance is decreased with renal impairment; thus, dosage adjustments are necessary in patients with renal impairment. Hepatic impairment has no effect on the pharmacokinetics of meropenem and therefore no dosing adjustment is necessary.