Pharmacokinetics and dosing regimen of meropenem in critically ill patients receiving continuous venovenous hemofiltration. 2000

T F Ververs, and A van Dijk, and S A Vinks, and P J Blankestijn, and J F Savelkoul, and J Meulenbelt, and F T Boereboom
Division of Hospital Pharmacy, University Medical Center Utrecht, The Netherlands.

OBJECTIVE To study the pharmacokinetics of meropenem in critically ill patients with acute renal failure receiving continuous venovenous hemofiltration (CWHF). METHODS Prospective, open-labeled study. METHODS Medical intensive care unit of the University Medical Center Utrecht. METHODS Five critically ill patients receiving CWHF for acute renal failure treated with meropenem for documented or suspected bacterial infection. METHODS All patients received meropenem (500 mg) administered intravenously every 12 hrs. Plasma samples and ultrafiltrate aliquots were collected during one dosing interval. RESULTS Mean age and body weight of the patients studied were 46.6 yrs (range, 28-61 yrs) and 85.8 kg (range, 70-100 kg), respectively. The following pharmacokinetic variables for meropenem were obtained: mean peak plasma concentration was 24.5 +/- 7.2 mg/L, mean trough plasma concentration was 3.0 +/- 0.9 mg/L, mean terminal elimination half-life was 6.37 +/- 1.96 hrs, mean total plasma clearance was 4.57 +/- 0.89 L/hr, mean CWHF clearance was 1.03 +/- 0.42 L/hr, mean nonrenal clearance was 3.54 +/- 1.06 L/hr, and mean volume of distribution was 0.37 +/- 0.15 L/kg. CONCLUSIONS In critically ill patients with acute renal failure, nonrenal clearance became the main elimination route. CWHF substantially contributed to the clearance of meropenem (23% of mean total plasma clearance). We recommend meropenem to be dosed at 500 mg intravenously every 12 hrs in patients receiving CWHF, according to our operational characteristics. This dosing regimen resulted in adequate trough plasma levels for susceptible microorganisms.

UI MeSH Term Description Entries
D007262 Infusions, Intravenous The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it. Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D008297 Male Males
D008657 Metabolic Clearance Rate Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D005260 Female Females
D006440 Hemofiltration Extracorporeal ULTRAFILTRATION technique without HEMODIALYSIS for treatment of fluid overload and electrolyte disturbances affecting renal, cardiac, or pulmonary function. Arteriovenous Hemofiltration,Venovenous Hemofiltration,Arteriovenous Hemofiltrations,Hemofiltration, Arteriovenous,Hemofiltration, Venovenous,Hemofiltrations,Venovenous Hemofiltrations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077731 Meropenem A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than IMIPENEM, but does not need to be given with an enzyme inhibitor such as CILASTATIN. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. 3-(5-Dimethylcarbamoylpyrrolidin-3-ylthio)-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo(3.2.0)hept-2-ene-2-carboxylic acid,Merrem,Penem,Ronem,SM 7338,SM-7338,SM7338
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

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