| DOI: 10.29090/psa.2024.03.24.AP0723 | Pharm Sci Asia 2024; 51(3), 241-249 |
Population Pharmacokinetic Modeling and Convenient Sampling of Midpoint Concentration for Therapeutic Drug Monitoring of Vancomycin in Vietnamese Pediatric PatientsLe Ba Hai1, Phung Chi Kien1, Nguyen Thi Dua3, Nguyen Trong Hao3, Vu Manh Hung4, Nguyen Thanh Hai1, Jennifer Le2, Nguyen Thi Lien Huong1*
1 Department of Clinical Pharmacy, Faculty of Pharmacology and Clinical Pharmacy, Hanoi University of Pharmacy, Hanoi, Vietnam
2
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, California, USA
3
Department of Pharmacy, Saint Paul Hospital, Hanoi, Vietnam
4
Department of Pharmacy, Thanh Hoa Pediatric Hospital, Thanh Hoa, Vietnam
(1) Background: Bayesian AUC-guided dosing of vancomycin is suggested for pediatric patients, preferably obtaining 2 concentrations with at least 1 trough concentration (ie. Peak and trough concentration - traditional sampling). However, this approach achieves optimal performance only when using a population pharmacokinetic (popPK) model of vancomycin suitable for the targeted population. Besides, obtaining 2 concentrations at the exact time in pediatrics poses challenges. This study aims to establish a popPK model of vancomycin in Vietnamese pediatric patients and explores the capability of Midpoint Concentration instead of traditional sampling; (2) Methods: This study included pediatric patients ≥ 3 months in two pediatric hospitals with a combined 2000 beds. The popPK analysis was performed by using a non-linear mixed-effect modeling approach with Monolix 2023R1®. Monte Carlo simulation was conducted using Simulx 2023R1® to explore if any Midpoint Concentration (Cmid) between Peak Concentration (Cpeak) and Trough Concentration (Ctrough) can replace traditional sampling in predicting the Area Under the Curve (AUC) of vancomycin; (3) Results and discussion: A total of 289 vancomycin concentrations from 98 patients with a median age of 1.86 [IQR 0.92 – 3.22] years, were included. The final model was as follows: CL (L/h) = 0.433*(BW/13.86)^0.777*(0.46/SCr)^0.83*(ln(age)/3.26)^2.16; and Vd (L) = 11.5*(BW/13.86)^0.777 (BW: kg, SCr: mg/dL, age: day). The internal validation demonstrated that the final model successfully described the observed data with bootstrap analysis, WRES, NPDE, and pcVPC plots showing good prediction performance. Compared to 2-point monitoring, the accuracy and precision of AUC calculating from Cmid were below 10% (4.6% and 5.7% respectively); (4) Conclusions: The popPK model of vancomycin in Vietnamese pediatric patients over 3 months old was well established, with body weight, age, and serum creatinine identified as significant covariates. A single concentration between peak and trough concentrations could be an feasible approach for dosing and monitoring vancomycin therapy in pediatrics.
Keyword:
Vancomycin; Vietnamese; Pediatric Patients; Population Pharmacokinetics (popPK); Midpoint Concentration
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