A New Pharmacokinetic Model of Propofol for Japanese Patients

Abstract

Target-controlled infusion (TCI) of propofol is used for general anesthesia. However, the only pharmacokinetic parameter commercially used for Japanese patients is weight, and pharmacokinetic models are based on European physical attributes. Drug metabolism also differs in races. This study aimed to identify optimal continuous doses of propofol for Japanese patients and to create a simulated pharmacokinetic (PK) model. Thirty Japanese patients were enrolled. Patients received a constant infusion of 9 mg/kg/h of propofol. Arterial blood samples were collected and the time course of plasma propofol concentrations was modeled using the nonlinear mixed effects model (NONMEM) three-compartmental PK model. We validated the model by intravenously injecting 10 patients with a TCI driver system programmed with the NONMEM model. Our model’s performance was evaluated using the median prediction error (MDPE), median absolute prediction error (MDAPE), and Wobble. We analyzed 320 blood samples for model building and 160 samples for validating our new model. The calculated parameters for the three-compartmental PK model were volume [V1, 3.58; V2, 13.0 + 0.49 × (Age—64); and V3, 186] and elimination clearance [CL1, 0.77 + (WT—54) × 0.04 + (HT—158) × 0.03; CL2, 0.89 + 0.12 × (Age—64); and CL3, 0.98 × exp ((Age—64)/10)]. The new model improved MDPE, MDAPE, and Wobble values (11.5% ± 43.8%, 14.3% ± 33.0%, and 25.0% ± 21.3%, respectively). We created a new pharmacokinetic model for Japanese patients, which is more accurate than the three existing models applied to Japanese populations. Electronic document is a “live” template. The various components of your paper [title, text, heads, etc.] are already defined on the style sheet, as illustrated by the portions given in this document.