Sign Out
Pharmacology: Pharmacodynamics: Mode of action: Meropenem is a carbapenem antibiotic for parenteral use, that is relatively stable to human dehydropeptidase-1 (DHP-1) and therefore does not require the addition of an inhibitor of DHP-1. Meropenem exerts bactericidal activity by inhibiting cell wall synthesis by penetrating the cell wall of most Gram-positive and Gram-negative bacteria to reach penicillin-binding-protein (PBP) targets. Its strongest affinity is toward PBPs 2, 3, and 4 of Escherichia coli and Pseudomonas aeruginosa and PBPs 1, 2 and 4 of Staphylococcus aureus. Bactericidal concentrations are typically one to two times the bacteriostatic concentrations; the exception is Listeria monocytogenes, against which lethal activity has not been observed.
Similar to imipenem, the antibacterial action of meropenem is related to binding of the drug to penicillin binding protein (PBPs) of Gram-positive and Gram-negative organisms. The high resistance of meropenem to most bacterial β-lactamases and good penetration of the drug through the outer membrane also contribute significantly to antimicrobial activity. Meropenem may be less of an inducer of β-lactamases than imipenem.
Pharmacokinetics: Absorption: Peak concentration: dependent on dose, renal function and administration technique. The time to peak concentration following intravenous administration is approximately 1 hour (range: 0.5-1.5 hours) after the start of the infusion.
Distribution: Plasma protein binding of meropenem is approximately 2%.
Meropenem achieves concentrations that match or exceed those required to inhibit most susceptible bacteria in most body fluids and tissues including cerebrospinal fluid. Peak concentrations in body fluids and tissues including cerebrospinal fluid. Peak concentrations in body fluids were mostly achieved in 1 hour following intravenous infusion.
The volume of distribution is 12 to 20 L.
Metabolism: Extrarenal, 20 to 25% increases up to 50% in patients with creatinine clearance of less than 20 ml/minute. There is one metabolite which is inactive, ICI-213689.
Excretion: Approximately 70% of a meropenem dose administered intravenously is recovered unchanged in the urine over 12 hours. The clearance of meropenem from plasma correlates with the creatinine clearance. There is no accumulation of repeated doses of meropenem 500 mg every 8 hours or 1 gram every 6 hours in patients with normal renal function. Dose adjustments are necessary in patients with renal impairment.
Elimination half-life: Adults and children age 2 years and older: 1 hour.
Children age 3 months to 2 years: 1.5 hours.
Preterm neonates (27 to 32 weeks gestational age, 21 days mean postnatal age): 3.4 hours.
Impaired renal function: 3.4 to 20 hours or longer.
