免疫抑制剤リボソーム化タクロリムスの開発と臓器移植における有用性の検討

Abstract

The tissue distribution and immunosuppressive efficacy of liposomal tacrolimus were investigated. For the pharmacokinetic study, 0.5mg/kg of tacrolimus was administrated to male Wistar rats intravenously as conventional intravenous (iv) formula (group A) or liposomal formula (group B). Changes in time of blood and tissue tacrolimus levels were compared between the two groups. Tacrolimus levels in the liver and spleen were significantly higher in group B than in group A (p＜0.05). On the contrary, tacrolimus levels in the kidney and brain were significantly lower in group B. In a canine liver transplantation model, 0.05mg/kg/day of liposomal tacrolimus for 14 days significantly prolonged allograft survival (MST: 202 days), in comparison to the same dose of tacrolimus as iv formula (MST: 24 days). In a canine allogeneic kidney transplantation, however, liposomal tacrolimus showed lower immunosuppressive efficacy (MST: 16 days) in comparison to iv formula (MST: 26 days). The difference of results between liver and kidney transplantation models suggests that local immunosuppressive effect in the liver allograft is the dominant mechanism of enhanced immunosuppressive efficacy of liposomal tacrolimus.