ABSTRACT
Objective To forward the concept of solution space of pharmacokinetics for studying radiophannaceutical distributions in animal models. Methods On the basis of special solutions of differential equations of pharmacokinetics, the solution space was established using the characteristics of linearly independent particular solutions and used to express the pharmacokinetics of pharmaceuticals in vivo. 0. 2 ml (7.4 MBq) 2β-carbomethoxy-3β- (4-corophenyl)-8-(2-18F-fluoroethyl) nortropane (18F-FECNT) was injected through tail vein into normal mice. The mice were sacrificed by decapitation at 5, 15, 30, 60, 120 and 180 min post-injection. Brain tissues were removed and weighed, and radioactivity was counted with the γ-counter. The solution space theory was used to study pharmacokinetics of 18F-FECNT in brain tissues of mice. Results The result showed that all solutions of pharmacokinetics models, based on differential equations, were included in the solution space. The solution of any organ or tissue could be linearly expressed by bases of the solution space. When the dimension number of the solution space was no more than 3, the solution could be directly expressed with coordinate picture. By this rule in our theory, the quantity of 18F-FECNT in brain tissues of mice changed with time, which was accorded with the experiment. The coordinates of striatum, frontal cortex, temporal cortex, occipital cortex, parietal cortex, hippocampus and cerebellum in the solution space were ( 10.13, 1.49), (4.27, 0. 84), (4.48, 0.81 ), (2.89, 0.98), (3.65, 0. 83),(3.55, 0. 98) and (2.03, 1.25 ), respectively. Conclusion The theory of solution space could be used to study pharmacokinetics of 18 F-FECNT in mice brain.
ABSTRACT
<p><b>AIM</b>To study the effect of recombinant hirudin (rH) on tPA-induced fibrinolysis and the possible mechanism of its action.</p><p><b>METHODS</b>The effect of rH on thrombin-fibrin complex (Th-Fn) was detected by 99mTc labeled rH. In the in vitro clot lysis, tPA as plasminogen activator, and recalcified plasma as plasminogen resource were used to study the influence of rH on fibrinolysis by detecting TAFIa, D-Dimer and FXIII.</p><p><b>RESULTS</b>In a canine model of femoral artery thrombosis, a clear radioactivity strip was imaged in 30 - 60 min on a part image, and the femoral vein thrombosis developed at 30 min. rH efficiently inhibited clot regeneration. Addition of TM could inhibit clot lysis obviously, and CPI could shorten the delay of clot lysis which due to TAFIa. There was a dose-dependent relationship with TM concentration and TAFI activation. FXIII activation was inhibited by low concentration of rH ( < or = 0.2 u x mL(-1)), and the level of fibrinolysis product, D-Dimer, increased.</p><p><b>CONCLUSION</b>rH could inhibit the thrombin binding to fibrin. rH inhibited the activation of TAFI and FXIII by combining with thrombin which resulted in enhancement of thrombolysis.</p>