Population Pharmacokinetics of Vancomycin in Kidney Transplant Recipients: Model Building and Parameter Optimization

Abstract

Background: Depending on the renal function of patients and many other influencing factors, studies on vancomycin pharmacokinetics show significant inter-and intraindividual variability. The present study was conducted using a population pharmacokinetics method to investigate the pharmacokinetic parameters and identified their influencing covariates for intravenous vancomycin in adult kidney transplant recipients. Methods:The drug monitoring data included 56 adult renal transplant recipients who received intravenous vancomycin as prophylactic medication. The analysis was performed by a population approach with NONMEM. Data were collected mainly during the first week after transplantation. Monitoring of vancomycin trough concentration in blood was initiated mainly 3-5 days after the initial administration. Results:The one-compartment open model was optimal and adequately described the data. Body weight (WT) and estimated glomerular filtration rate (GFR) were identified as significant covariates of the pharmacokinetic parameters CL and V of intravenous vancomycin in the kidney transplant patients. The typical values of vancomycin CL and V were 2.08 L h -1 and 63.2 L, respectively. A dosage strategy scheme according to model results was also designed. Conclusion:Both WT and GFR of the kidney transplant patients positively influence the pharmacokinetic parameters CL and V for intravenous vancomycin. Our population

Population Pharmacokinetics and Model-Based Dose Optimization of Vancomycin in Sudanese Adult Patients with Renal Impairment

“… 7 The estimated CL (2.02 L/h) was nearly identical to what is seen in other population studies. 19 , 22 , 23 The typical value of V (65 L) was comparable to previously reported values. 18 , 22 , 24 During the covariate selection process, the OFV value decreased by 50.22 points (p>0.001) when CLcr was added to the model.…”

“… 19 , 22 , 23 The typical value of V (65 L) was comparable to previously reported values. 18 , 22 , 24 During the covariate selection process, the OFV value decreased by 50.22 points (p>0.001) when CLcr was added to the model. Previous studies have reported serum creatinine CLcr as an important covariate explaining BSV in vancomycin’s CL.…”

“…CLcr was predominantly included as an important influential covariate on vancomycin CL in previous population models. 22,23,[28][29][30][31] Most of the reported vancomycin population pharmacokinetics (PPK) models used CLcr calculated by the Cockcroft-Gault formula, which is influenced by age, weight, sex, and SCR. 7 The data lacked some patient information, such as body weight and height, which made the calculation of creatinine clearance using the Cockcroft-Gault equation not possible.…”

Initial sirolimus dosage recommendations for pediatric patients with PIK3CD mutation-related immunodeficiency disease

“…In actual practice, conditional WRES is usually with FOCE-I, and of course this is acceptable. Thus, conditional WRES are all with FOCE-I in the following: Jing et al’s ( 2021 ) pharmacokinetic analysis and dosing guidelines for tacrolimus co-administration with wuzhi capsules in Chinese renal transplant recipients; Li et al’s (2021 ) study of dose tailoring of tacrolimus, based on a non-linear pharmacokinetic model in children with refractory nephrotic syndrome; Yu et al’s (2021 ) study of pharmacokinetics and optimization of polymyxin B dosing in adult patients with various renal functions; Ma et al’s (2020 ) study of the pharmacokinetics of vancomycin in kidney transplant recipients; and Cai et al’s (2020 )model building and parameter optimization in pharmacokinetics and dosing regimen optimization of tacrolimus in Chinese lung transplant recipients.…”

Dose optimization of vancomycin in obese patients: A systematic review

“…These guidelines recommend dosing strategy and monitoring of vancomycin treatment in obese patients in a manner similar to non-obese patients (Durand et al, 2018). Multisite studies have been documented the PK parameters of vancomycin in non-obese patients (Katip et al, 2016;Ma et al, 2020;Arjangpour et al, 2022). However, the data among obese patient is limited.…”