科研之友
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摘要
Eighteen healthy volunteers were randomly assigned to receive a single intravenous injection of 0.5 or 0.75 mg/kg bivalirudin (2 groups, n = 9 per group). Plasma concentrations were determined by LC/MS/MS and pharmacological effects, including activated partial thromboplastin time (APTT) and prothrombin time (PT) were measured simultaneously. The experimental data were quantitatively analyzed according to the PK-PD model construct. The pharmacokinetic profiles of bivalirudin conformed to a two-compartment model. The effects of APTT and PT directly connected with the plasma drug concentration and showed no hysteresis. The relationship between the plasma concentrations and the effects of APTT and PT could be represented by the sigmoid E-max model. The E-max values for APTT and PT were 145.20 +/- 32.58 and 32.45 +/- 8.58 S, E-0 values were 29.07 +/- 0.64 and 11.82 +/- 0.57 S, and the EC50 values were 3.89 +/- 1.93 and 3.07 +/- 2.05 mg/L, respectively. The results based on the PK-PD modeling showed that 0.75 mg/kg intravenous bolus followed by 2.5 mg/kg/h infusion is a suitable dose regiment for bivalirudin during the surgery. The PK-PD model of bivalirudin was developed in healthy Chinese adult subjects, and may provide a more rational basis for dose optimizing in the clinical practice.
