Pharmacokinetics of Nalmefene hydrochloride in healthy volunteers / 重庆医科大学学报

ABSTRACT

Objective:To study the phamacokinetics of Nalmefene hydrochloride. Methods:30 healthy Chinese volunteers were assigned to 3 groups according to randomized design, and each group were given respectively a single intravenous administration dose of 0.5 mg, 1mg and 2mg of Nalmefene hydrochloride. The electrospray ionization positive selected reaction monitoring detections for Nalmefene hydrochloride and allyln-oroxymorphone (the internal standard) in the plasma and in the urine were used. The pharmaceutical parameters were calculated by 3P87 software. Results: The limit of the detection for Nalmefene hydrochloride was 0.0008 ng/ml in plasma and 0.0003 ng/ml in urine. There were good linear relationship range from 0.04 to 625ng/ml in plasma and 0.2 to 625 ng/ml in the urine. The variation coefficient in day and days, and the recoveries fitted the clinical pharmacokinetic study requirements. After a single intravenous administration of 0.5 mg,1mg, and 2mg of Na-lmefene hydrochloride, the obtained pharmacokinetic parameters were respectively as follows:Cmax were(1.74?0.48)?g/L,(4.17?1.08) ?g/L,(7.88?2.89) ?g/L;t1/2? were(12.83?3.98) h,(12.6?6.4) h, (10.58?3.74) h;V were (3.45?0.16) L/kg;(4.11?0.0716)L/kg、(4.25?0.56)L/kg;CL were (0.81?0.11) L/(h?kg), (0.85?0.15)L/(h?kg), (0.87?0.11) L/(h?kg);AUC0-∞ were (21.62?9.34) (ng/L)*h,(24.89?8.52) (ng/L)*h, (35?11.2) ng/L)*h;the urine accumulatived exc-retory rate were (78?21)%,(71?29)%,(78?19)%. Conclusion: The determination method for Nalmefene hydro-chloride in the plasma and in the urine by the electrosprayionization positive selected reaction monitoring detections is exclusive, accurate, sensitive and suitable. Pharmacokinetic characteristics in 3 groups of human treated with intravenous administration were described by a two-compartment model. The pharmaceutical characteristics of doxycycline hydrochloride in human body were linear in the range of 0.5~2.0 mg.