Population pharmacokinetic/pharmacodynamic modeling of nifekalant injection with varies dosing plan in Chinese volunteers: a randomized, blind, placebo-controlled study

In this study, a single-center, randomized, blind, dose-ascending, placebo-controlled study was conducted to explore the intrinsic characteristics of nifekalant injection in healthy Chinese volunteers by a population pharmacokinetic (PK)-pharmacodynamic (PD) model approach. 42 subjects were enrolled in this study and received one of three dose plans (loading dose on Day 1 (0.15, 0.3 or 0.5 mg/kg), loading dose followed by maintenance dose (0.2, 0.4 or 0.8 mg/kg/h) on Day 4) or vehicle. Blood sampl es were drawn for PK evaluation, and ECGs were recorded for QTc calculation at the designed timepoints. No Torsades de Pointes occurred during the study. The popPK model of nifekalant injection could be described by a two-compartment model with first-order elimination. The population mean clearance (CL) was 53.8 L/h. The population mean distribution volume of the central (Vc) and peripheral (Vp) compartments was 8.27  L and 45.6 L, respectively. A nonlinear dose–response (Emax) model well described the pharmacodynamic effect (QTc interval prolongation) of nifekalant. The Emax and EC50 from current study were 101  ms and 342 ng/mL, respectively.
Source: Journal of Pharmacokinetics and Pharmacodynamics - Category: Drugs & Pharmacology Source Type: research