Dosage Optimization of Meropenem in South Indian Sepsis Patients using Pharmacometrics Approach

Abstract

Aim: Sepsis patients are more prone to have sub-therapeutic drug concentrations and so treatment failures. Non optimized dosage regimen of antibiotics is one of the prime reasons why the prevalence of antibiotic resistance is rising. This study aimed to propose optimized dosage regimen for Meropenem in sepsis patients using the pharmacometric approach. Methods: Prospective open label study was conducted among 58 south Indian adult Sepsis patients received Meropenem 1g over 30 mins or 3-hour infusion every 8h or 12h. The plasma samples were collected from the patients using window sampling (1-8 h) and concentration of Meropenem was quantified using RP-HPLC. Population pharmacokinetics analysis and simulations were performed using PUMAS® v.1.40.1. Results: Two compartment model with first order elimination best described the data and the total clearance (CL), inter-compartmental clearance (Q), volume of the central compartment (Vc), volume of the peripheral compartment (Vp) were 4.46 L/hr & 13.29 L/h and 47.16 L & 26.55 L respectively. The most significant covariate that influenced the Meropenem Clearance was creatinine clearance. The additive error was 0.0021 mg/L and the proportional error was 15.6%. Meropenem administered over 3 h infusion was observed to be superior than 30 min infusion by simulation studies. Conclusion: Renal function of the patients significantly influence the clearance of Meropenem and infusion over 3 h is found to be superior than 30 min in terms of attaining the trough concentration of 8 mg/L. Additionally, therapeutic drug monitoring of Meropenem in these patients will aid in the optimization of Meropenem dosing regimen.