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[3H]-메토트렉세이트-락토오스아미노화한 소 혈청 알부민 공유결합체의 간표적성 및 체내동태
김종국(Chong Kook Kim),이응두(Woong Doo Lee),박호군(Ho Koon Park) 대한약학회 1992 약학회지 Vol.36 No.6
The organ distribution of [3H]-methotrexate-lactosaminated bovine serum albumin conjugates ([3H]-MTX-LBSA) was investigated to examine their role as a liver-specific anticancer drug. Synthesis of lactosaminated bovine serum albumin(LBSA) with BSA, lactose and sodium cyanoborohydride through reductive animation was followed by its conjugation with methotrexate (MTX) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), thereby synthesizing [3H]-MTX-LBSA conjugates. Organ distribution and plasma elimination profiles were studied in male Wistar rats after intravenous injection of [3H]-MTX-LBSA conjugates. The fates of [3H]-MTX and the [3H]-MTX-BSA conjugates fates were also investigated for comparison. The results showed that the plasma level of [3H]-MTX-LBSA conjugates declined more rapidly than those of [3H]-MTX-BSA and their liver concentration was significantly higher than those of other treatment (p<0.01). In addition, their uptake compared to the amount taken up by the liver (1 : 33.1 at 10min, 1 : 24.1 at 120min). All these suggested that MTX-LBSA conjugate is one of the drug delivery system (DDS) that is advanced in concentrating MTX in the liver and minimizing the renal toxicity of MTX.