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Population Pharmacokinetics and Target Attainment of Meropenem in Plasma and Tissue of Morbidly Obese Patients after Laparoscopic Intraperitoneal Surgery
- Source :
- Antimicrobial Agents and Chemotherapy. 59:6241-6247
- Publication Year :
- 2015
- Publisher :
- American Society for Microbiology, 2015.
-
Abstract
- Meropenem serves as a clinically important, broad-spectrum antibiotic. While meropenem is commonly used in obese patients, its pharmacokinetics in this patient group is not well known. Our aim was to characterize the population pharmacokinetics and target attainment in plasma, subcutaneous tissue, and peritoneal fluid for meropenem in morbidly obese patients. Four doses of 1g meropenem were given as 15-min infusions every 8 h to five morbidly obese patients (body mass index [BMI], 47.6 to 62.3 kg/m 2 ). After the fourth dose, serial meropenem concentrations were determined in plasma and, via microdialysis, in subcutaneous tissue and peritoneal fluid. All concentrations were analyzed simultaneously via population modeling, and target attainment probabilities predicted via Monte Carlo simulations using the target of unbound meropenem concentrations above the MIC for at least 40% of the dosing interval. For patients with 53 kg fat-free mass, total clearance was 18.7 liters/h and volume of distribution at steady state was 27.6 liters. The concentrations in subcutaneous tissue and peritoneal fluid largely paralleled those in plasma (equilibration half-life, 90% after 1 g meropenem every 8 h as a 15-min infusion for MICs of up to 2 mg/liter in plasma and peritoneal fluid and 0.5 mg/liter in subcutaneous tissue. Meropenem pharmacokinetics in plasma and peritoneal fluid of obese patients was predictable, but subcutaneous tissue penetration varied greatly. (This study has been registered at ClinicalTrials.gov under registration no. NCT01407965.)
- Subjects :
- Adult
Male
Microdialysis
medicine.medical_specialty
Population
Biological Availability
Microbial Sensitivity Tests
Meropenem
Subcutaneous Tissue
Pharmacokinetics
medicine
Ascitic Fluid
Humans
Pharmacology (medical)
Prospective Studies
education
Peritoneal Cavity
Pharmacology
Volume of distribution
education.field_of_study
business.industry
Peritoneal fluid
Middle Aged
Anti-Bacterial Agents
Obesity, Morbid
Surgery
Infectious Diseases
medicine.anatomical_structure
Area Under Curve
Pharmacodynamics
Injections, Intravenous
Female
Laparoscopy
Thienamycins
business
Monte Carlo Method
Half-Life
medicine.drug
Subcutaneous tissue
Subjects
Details
- ISSN :
- 10986596 and 00664804
- Volume :
- 59
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy
- Accession number :
- edsair.doi.dedup.....e16c136acea8e29dd6a62c81348315a2
- Full Text :
- https://doi.org/10.1128/aac.00259-15