Population pharmacokinetics of arginine glutamate in healthy Chinese volunteers

1. The present study developed population pharmacokinetic models of arginine and glutamate in healthy Chinese volunteers. Two nonlinear mixed-effect models were developed using NONMEM® software (ICON Development Solutions, Ellicott City, MD) to describe the pharmacokinetic properties and to assess the relevant parameters as well as the inter-individual variability. The potential covariates were screened using stepwise approach and the stability and predictive capability of the models were performed using bootstrap and visual predictive check. 2. The concentration time curves of arginine and glutamate were best described by a first-order elimination two-compartment model and a nonlinear elimination one-compartment model, respectively. The final parameter estimation of arginine for CL was 44.1 L/h. Q, V₁ and V₂ were 23 L/h, 20.3 L and 46 L, respectively. The final parameter estimation of glutamate for V_max and K_m were 18.8 mg/h and 77.2 mg/L, respectively. V for low dose and high dose was 23.1 L and 36.3 L, respectively. 3. For arginine, weight was significant covariate on the apparent distribution volume of peripheral compartment. The gain in weight remarkably increases V_2. For glutamate, dose as a significant covariate on the apparent distribution volume was included, subjects received high dose (20 g) have remarkably higher V compared to subjects received low dose (10 g).