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

BACKGROUND: 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). MATERIALS AND METHODS: 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 1,000 mg q8h and 1,500 mg q12h over 3-hour infusion were performed based on the renal status of the patients. RESULTS: A two-compartment model was used for popPK analysis, and the values of the pharmacokinetic parameters for CL, V1, V2, and Q were 12.2 L/h, 21.7 L, 7.74 L, 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 1,000 mg q8h produced better results if CRCL was > 100 mL/min. CONCLUSION: 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.

Population pharmacokinetics of ciprofloxacin in Pakistani patients suffering from enteric fever.

BACKGROUND: Ciprofloxacin, a potent carboxy-fluoroquinolone is proved to be effective against some resistant strains of Gram-negative bacteria. Being a hydrophilic drug, it is primarily excreted through the kidney; almost 66% of the clearance from the body occurs through glomerular filtration. Therefore, renal status of the patient can have a significant effect on ciprofloxacin clearance. MATERIALS AND METHODS: A total of 158 samples were collected from 32 patients treated with ciprofloxacin in the Surgical Unit-I of Lahore General Hospital, Pakistan. The data was used for the development of a population pharmacokinetic model by using non-linear mixed-effect modeling (NONMEM) software. The influence of different covariates (age, sex, body weight, serum creatinine (SeCR), and creatinine clearance (CRCL)) was observed on ciprofloxacin clearance (CL) and volume of distribution (Vd) by stepwise covariate modeling (SCM). RESULTS: A one-compartment model was used for ciprofloxacin population pharma-cokinetik (popPK) analysis, and the values for ciprofloxacin CL and Vd in the final model were estimated at 19.8 L/h and 74.9 L, respectively. Among all the tested covariates, only CRCL was proven to have significant influence on ciprofloxacin CL. CONCLUSION: A strong relationship was found between the ciprofloxacin CL and renal status of the patients. The model can be used for dose tailoring in patients based on their CRCL values before the start of therapy with ciprofloxacin among Pakistani patients.