Abstract
Purpose. Tacrolimus (FK 506) is a new potent immunosuppressant. Because of poor water solubility, the conventional intravenous dosage forms of FK 506 (C-FK 506) contain surfactants such as HCO-60 which may cause adverse effects. We sought a liposomal formulation of FK 506 (L-FK 506) containing endogenous phospholipids to target drug to the spleen, a major organ controlling the immune system.
Methods. L-FK 506, consisting of 0.1 µm diameter vesicles of phosphatidylcholine and phosphatidylglycerol (molar ratio 9:1) and 7.5 mole% drug, was evaluated for in vitro stability. The intravenous disposition profile, spleen distribution, and immunosuppression of L-FK 506 was compared with that of C-FK 506 in the rat after single doses of 0.3 mg/kg.
Results. The L-FK 506 showed good in vitro stability. L-FK 506 exhibited an increased volume of distribution at steady-state (Vss) (from 3.41 to 14.71 L/kg) and increased mean residence time (MRT) (from 2.83 to 16.07 hr). FK 506 concentrations in spleen were increased by 40% at 10 hr after administration of the liposomal formulation. The pharmacodynamics of L-FK 506, evaluated by the extent of inhibition of splenocyte proliferation, was comparable to that of C-FK 506.
Conclusions. Liposomal FK 506 may be an improved dosage form for parenteral use.
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Lee, MJ., Straubinger, R.M. & Jusko, W.J. Physicochemical, Pharmacokinetic and Pharmacodynamic Evaluation of Liposomal Tacrolimus (FK 506) in Rats. Pharm Res 12, 1055–1059 (1995). https://doi.org/10.1023/A:1016222817860
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DOI: https://doi.org/10.1023/A:1016222817860