Population pharmacokinetics of meropenem among post-operative patients in Pakistan.

Abstract

Meropenem, a potent carbapenem is considered the first choice for the empirical treatment of severe infections. Being a hydrophilic drug, more than 83% of the administered dose is eliminated through the renal route, and therefore, the kidney status of the patient may have a significant effect on meropenem clearance (CL). The data of 205 samples obtained from 59 patients treated with meropenem at the General Hospital Lahore, Pakistan, was used for the development of a population pharmacokinetic (-popPK) model by using nonlinear mixed-effects modeling software. The effect of age, body weight, creatinine clearance (CRCL), and gender was observed on meropenem CL through a stepwise covariate modeling approach. Simulations of 1,000mg q8h and 1,500mg q12h over 3-hour infusion were performed based on the renal status of the patients. A two-compartment model was used for popPK analysis, and the values of the pharmacokinetic parameters for CL, V1, V2, and Q were 12.2L/h, 21.7L, 7.74L, and 3.28 L/h, respectively. Meropenem CL was significantly influenced by CRCL, while no significant effect of body weight, age, and sex was observed. Both simulated dosage regimens were equally effective if CRCL of the patient was ≤100 mL/min, while 1,000mg q8h produced better results if CRCL was >100 mL/min. The CL of meropenem depends on the renal status of the patients. The model can be used for dosing simulations based on the CRCL of the patients in order to tailor the dose of meropenem in Pakistani patients.