摘要：KW-3902 (a newly synthesized adenosine A1-receptor antagonist) has potent diuretic and renal protective activities. We investigated the influence of the emulsion formulation on the pharmacokinetics of KW-3902 and its metabolite (M1) in rats using three different formulations, i.e. , a lipid emulsion about 130 nm in diameter composed of egg yolk lecithin: soybean oil: oleic acid=1 : 1 : 0.048, a liposome about 100 nm in diameter composed of egg yolk lecithin, and a saline solution containing 1% (v/v) each of dimethyl sulfoxide and 1 n NaOH. There was no significant difference in the pharmacokinetic parameters of KW-3902 (elimination half-life ( T 1/2), area under the plasma concentration–time curves ( AUC 0—∞), total body clearance ( CL ), mean residence time ( MRT ) and volume of distribution at steady-state ( V dss)) and M1 ( C max, T 1/2, AUC 0—∞ and MRT ) after injection of these three dosage forms. Moreover, we investigated in vitro the binding of KW-3902 to blood components using these three formulations. KW-3902 was completely partitioned into the blood components regardless of its dosage form. These findings suggested that KW-3902 dissociated rapidly from the lipid emulsion or liposome in blood after injection and showed intrinsic pharmacokinetics of KW-3902 at doses of 0.1 and 1 mg/kg. Thus, the lipid emulsion formulation of KW-3902 was defined as a solvent, which was a vehicle for dissolving the drugs to prepare the injection, at its expected effective doses.
