Population Pharmacokinetics and Pharmacodynamics of Meropenem in Nonobese, Obese, and Morbidly Obese Patients

Abstract

The study objective was to evaluate meropenem population pharmacokinetics and pharmacodynamics in nonobese, obese, and morbidly obese patients. Forty adult patients-11 nonobese (body mass index [BMI] < 30 kg/m ), 9 obese (30 kg/m ≤ BMI < 40 kg/m ), and 20 morbidly obese (BMI ≥ 40 kg/m )-received meropenem 500 mg every 6 hours (q6h), q8h, or q12h or 1 g q6h or q8h, infused over 0.5 hour. Population pharmacokinetic modeling was performed using NONMEM, and 5000-patient Monte-Carlo simulations were performed to calculate probability of target attainment (PTA) for 5 dosing regimens, infused over 0.5 and 3 hours, using fT>MIC of 40%, 54%, and 100% of the dosing interval. A 2-compartment linear-elimination model best described the serum concentration-time data, and creatinine clearance was significantly associated with systemic clearance. Pharmacokinetic parameters were not significantly different among patient groups. In patients with creatinine clearances ≥50 mL/min, all simulated dosing regimens achieved >90% PTA at 40% fT>MIC in all patient groups at MICs ≤2 mg/L. Only 500 mg q8h, infused over 0.5 hour, did not achieve >90% PTA at 54% fT>MIC in nonobese and morbidly obese patients. At 100% fT>MIC, 1 g q6h and 2 g q8h, infused over 3 hours, reliably achieved >90% PTA in all patient groups. Meropenem pharmacokinetics are comparable among nonobese, obese, and morbidly obese patients. Standard dosing regimens provide adequate pharmacodynamic exposures for susceptible pathogens at 40% and 54% fT>MIC, but prolonged infusions of larger doses are needed for adequate exposures at 100% fT>MIC. Dosage adjustments based solely on body weight are unnecessary.

Population pharmacokinetics of standard-dose meropenem in critically ill patients on continuous renal replacement therapy: a prospective observational trial

“…3). The majority of the mean PK parameter estimates obtained in our study were in agreement with the ones obtained by other authors and are presented in Table 3 [4, [15][16][17][18][19][20]. The typical clearance values are similar, yet the volume of distribution at steady state (Vss = V 1 + V 2 ) is not consistent between the studies.…”

“…Since recommended beta-lactam regimens are often inadequate in septic patients treated with CRRT, the drug concentrations might be too low to ensure adequate bacterial killing, resulting in increased morbidity and mortality, as well as the emergence of antibiotic resistance. Despite numerous studies on meropenem pharmacokinetics in the critically ill patients published to date, there is no consensus on dosing of this widely used antimicrobial in different ICU scenarios [4,[15][16][17][18][19][20]. In this observational single-center cohort study, performed at a tertiary mixed ICU, we aimed to characterize the sources of PK variability of meropenem in a diverse population of critically ill patients receiving CRRT and to perform dosing simulations to assess their probability of target attainment (PTA), in order to provide empirical dosing recommendations.…”

Effects of uric acid, creatinine clearance, and infusion duration on the population pharmacokinetics of meropenem in critically ill patients

“…Adela et al found that the administration of 2000 mg/8 h of meropenem as a continuous infusion allowed higher serum meropenem concentrations [35]. Similar results were found in other studies of meropenem [14,16,34,35,37].…”

Comprehensive Guidance for Antibiotic Dosing in Obese Adults

“…Obesity increased meropenem Vd and Cl in both critically ill and noncritically ill patients, but these differences did not hinder achievement of standard PD targets (Table ). PTA was generally high (greater than 80%) and similar in obese and nonobese critically ill patients, and greater than 90% in other hospitalized populations at an MIC of 2 mg/L, the susceptibility breakpoint for P. aeruginosa . One study showed high meropenem tissue penetration in five morbidly obese patients undergoing abdominal surgery (AUC ratio of 0.943 and 0.721 in peritoneal and subcutaneous tissue, respectively) (Table ).…”