Meropenem clinical pharmacology: Difference between revisions
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At the end of a 30-minute intravenous infusion of a single dose of MERREM I.V. in normal | __NOTOC__ | ||
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 | {{Meropenem}} | ||
MERREM I.V. in normal volunteers results in mean peak plasma concentrations of approximately | {{CMG}} | ||
45 µg/mL (range 18-65) for the 500 mg dose and 112 µg/mL (range 83-140) for the 1 g dose. | |||
==Clinical Pharmacology== | |||
Following intravenous doses of 500 mg, mean plasma concentrations of meropenem usually decline to | |||
approximately 1 µg/mL at 6 hours after administration. | 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. | ||
In subjects with normal renal function, the elimination half-life of MERREM I.V. is approximately 1 | Following intravenous doses of 500 mg, mean plasma concentrations of meropenem usually decline to approximately 1 µg/mL at 6 hours after administration. | ||
hour. Approximately 70% of the intravenously | In subjects with normal renal function, the elimination half-life of MERREM I.V. is approximately 1 hour. Approximately 70% of the intravenously | ||
meropenem in the urine over 12 hours, after which little further urinary excretion is detectable. Urinary | |||
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. | |||
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%. | Plasma protein binding of meropenem is approximately 2%. | ||
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There is one metabolite that is microbiologically inactive. | There is one metabolite that is microbiologically inactive. | ||
Meropenem penetrates well into most body fluids and tissues including cerebrospinal fluid, achieving | 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 | ||
concentrations matching or exceeding those required to inhibit most susceptible bacteria. After a single | 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. | ||
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)''' | |||
{| | |||
|- | |||
|[[File:Meropenem Concentrations.jpg|thumb|800px|left|thumb|400px|left]] | |||
|- | |||
|} | |||
*at 1 hour unless otherwise noted | *at 1 hour unless otherwise noted | ||
†obtained from blister fluid | †obtained from blister fluid<BR> | ||
‡in pediatric patients of age 5 months to 8 years | ‡in pediatric patients of age 5 months to 8 years <BR> | ||
§in pediatric patients of age 1 month to 15 years | §in pediatric patients of age 1 month to 15 years <BR> | ||
The pharmacokinetics of MERREM I.V. in pediatric patients 2 years of age or older are essentially | 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 | ||
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. | 10 to 40 mg/kg. | ||
Pharmacokinetic studies with MERREM I.V. in patients with renal insufficiency have shown that the | 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. | ||
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 | Meropenem I.V. is hemodialyzable. However, there is no information on the usefulness of hemodialysis to treat overdosage. (See OVERDOSAGE.) | ||
hemodialysis to treat overdosage. (See OVERDOSAGE.) | |||
A pharmacokinetic study with MERREM I.V. in patients with hepatic impairment has shown no | A pharmacokinetic study with MERREM I.V. in patients with hepatic impairment has shown no effects of liver disease on the pharmacokinetics of meropenem. | ||
effects of liver disease on the pharmacokinetics of meropenem. | |||
Revision as of 21:42, 20 December 2013
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)
 |
- 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.