Population Pharmacokinetics and Target Attainment of Meropenem in Plasma and Tissue of Morbidly Obese Patients after Laparoscopic Intraperitoneal Surgery
| Autor: | Anna Maria Wolf, Juergen B. Bulitta, Claas Brockschmidt, Max Kurlbaum, Mathias Wittau, Evelyn Hemper, Jan Scheele, Doris Henne-Bruns |
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| Rok vydání: | 2015 |
| Předmět: |
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 |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 59:6241-6247 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.00259-15 |
| Popis: | 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.) |
| Databáze: | OpenAIRE |
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