Abstract：
: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 4 h 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 which 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.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Ohzawa N,Takahashi Y,Ogihara T,Nakai Y,Ishiguro Jdoi
10.1248/bpb.20.732subject
Has Abstractpub_date
1997-07-01 00:00:00pages
732-8issue
7eissn
0918-6158issn
1347-5215journal_volume
20pub_type
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