OBJECTIVETo investigate the pharmacokinetics of nalmefene after intravenous administration at a single or multiple doses in Chinese healthy volunteers.

METHODSThis open, randomized clinical trial involved 12 healthy volunteers, who received a single-dose (2 mg) nalmefene injection. Before and at different time points after the injection, blood sample were obtained from the subjects. After the single intravenous dose trial, 8 healthy volunteers received intravenous nalmefene at 2 mg once daily for 6 consecutive days, and the plasma drug concentrations were determined on the morning of days 4, 5 and 6 using liquid chromatography/tandem mass spectrometry and the pharmacokinetic parameters were calculated using PKS program.

RESULTSThe main pharmacokinetic parameters of nalmefene (Cmax, Tmax, T1/2, AUC0-48, and AUC0-infinity) after the single intravenous dose were 7.34-/+1.56 microg/L, 0.08 h, 12.01-/+2.20 h, 30.29-/+9.84 microg.L(-1).h, and 32.23-/+9.94 microg.L(-1).h, respectively; the parameters after multiple doses were 8.04-/+1.09 microg/L, 0.08 h, 12.43-/+1.44 h, 33.64-/+9.15 microg.L(-1).h and 35.98-/+9.23 microg.L(-1).h, respectively. The steady-state pharmacokinetic parameters including the degree of fluctuation (DF), AUCss and Cav were 4.69-/+1.29, 19.64-/+6.20 microg.L(-1).h and 1.64-/+0.52 microg/L, respectively.

CONCLUSIONNalmefene showed similar pharmacokinetics in Chinese healthy volunteers with those in the foreign testees, and can be safely administered in healthy volunteers without producing unmanageable pain.