Metabolic Fate of Ulinastatin (2); Pharmacokinetics in Rabbits Following Intra-Articular Administration.

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  • Metabolic Fate of Ulinastatin 2 Pharmac

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The absorption and distribution of ulinastatin following intra-articular administration of [125I]ulinastatin to rabbits were determined and kinetic analysis using a multi-compartment model was performed. At 4h after administration, the content of radioactivity in the synovial fluid, which was comparable to that of the immunoreactive ulinastatin, was 14.51% of the dose and decreased in a biphasic manner. The highest level of radioactivity was observed in the synovial membrane, followed by the meniscus, ligament, cartilage and patella, the radioactivities of whcih also declined biphasically. After intra-articular administration, the plasma concentration of total radioactivity increased slowly and reached maximum at 4.3 h, and then declined slowly in a monophasic manner with a half-life of 10.8 h. The radioactivity of the high molecular weight fraction in plasma, which reached maximum at 1.7 h after administration and then declined with a half-life of 11.8 h, was consistent with the time curve for immunoreactive ulinastatin in the plasma through 24 h after the administration. Within 8 and 24 h after administration, respectively, 1.48 and 4.66% of the administered radioactivity were transferred to the lymphatic fluid. The pharmacokinetics of[125I]ulinastatin after an intra-articular administration could be explained using a multi-compartment model in which a portion of the administered ulinastatin was absorbed via the lymphatic system. This finding suggested that ulinastatin was rapidly distributed and retained for a long period of time in the joint tissues. In addition, the pharmacokinetics of ulinastatin following intra-articular administration indicated typical flip-flop kinetics.

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