Meropenem clinical pharmacology

Meropenem
MERREM® FDA Package Insert
Description
Clinical Pharmacology
Microbiology
Indications and Usage
Contraindications
Warnings
Precautions
Adverse Reactions
Overdosage
Clinical Studies
Dosage and Administration
Compatibility, Reconstitution, and Stability
How Supplied
Labels and Packages

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Clinical Pharmacology

At the end of a 30-minute intravenous infusion of a single dose of MERREM I.V. in normal volunteers, mean peak plasma concentrations are approximately 23 µg/mL (range 14-26) for the 500 mg dose and 49 µg/mL (range 39-58) for the 1 g dose. A 5-minute intravenous bolus injection of MERREM I.V. in normal volunteers results in mean peak plasma concentrations of approximately 45 µg/mL (range 18-65) for the 500 mg dose and 112 µg/mL (range 83-140) for the 1 g dose.

Following intravenous doses of 500 mg, mean plasma concentrations of meropenem usually decline to approximately 1 µg/mL at 6 hours after administration. In subjects with normal renal function, the elimination half-life of MERREM I.V. is approximately 1 hour. Approximately 70% of the intravenously

administered dose is recovered as unchanged meropenem in the urine over 12 hours, after which little further urinary excretion is detectable. Urinary concentrations of meropenem in excess of 10 µg/mL are maintained for up to 5 hours after a 500 mg dose. No accumulation of meropenem in plasma or urine was observed with regimens using 500 mg administered every 8 hours or 1 g administered every 6 hours in volunteers with normal renal function.

Plasma protein binding of meropenem is approximately 2%.

There is one metabolite that is microbiologically inactive.

Meropenem penetrates well into most body fluids and tissues including cerebrospinal fluid, achieving concentrations matching or exceeding those required to inhibit most susceptible bacteria. After a single intravenous dose of MERREM I.V., the highest mean concentrations of meropenem were found in tissues and fluids at 1 hour (0.5 to 1.5 hours) after the start of infusion, except where indicated in the tissues and fluids listed in the table below.

Meropenem Concentrations in Selected Tissues

(Highest Concentrations Reported)

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• at 1 hour unless otherwise noted

†obtained from blister fluid
‡in pediatric patients of age 5 months to 8 years
§in pediatric patients of age 1 month to 15 years

The pharmacokinetics of MERREM I.V. in pediatric patients 2 years of age or older are essentially similar to those in adults. The elimination half-life for meropenem was approximately 1.5 hours in pediatric patients of age 3 months to 2 years. The pharmacokinetics are linear over the dose range from 10 to 40 mg/kg.

Pharmacokinetic studies with MERREM I.V. in patients with renal insufficiency have shown that the plasma clearance of meropenem correlates with creatinine clearance. Dosage adjustments are necessary in subjects with renal impairment. (See DOSAGE AND ADMINISTRATION - Use in Adults with Renal Impairment.) A pharmacokinetic study with MERREM I.V. in elderly patients with renal insufficiency has shown a reduction in plasma clearance of meropenem that correlates with age-associated reduction in creatinine clearance.

Meropenem I.V. is hemodialyzable. However, there is no information on the usefulness of hemodialysis to treat overdosage. (See OVERDOSAGE.)

A pharmacokinetic study with MERREM I.V. in patients with hepatic impairment has shown no effects of liver disease on the pharmacokinetics of meropenem.

References

Adapted from the FDA Package Insert.