A comparative study of pharmacokinetics of recombinant prourokinasein subconjunctival and drip methods of administration

Purpose: to compare the dynamics of recombinant prourokinase (RPU) in humor of the anterior chamber of the eye with regard to administration technique (instillations vs. subconjunctival injection) using fluorescent spectrophotometry. Material and methods. 62 samples of anterior chamber humor were obtained from 62 patients (62 eyes) who underwent cataract surgery, with rigid pupil due exfoliation syndrome or after an earlier acute iridocyclitis. The patients were divided into two groups. Group 1 received the medication by forced instillations of RPU solution with the concentration of 330 IU per 1 ml of 0.9 % sodium chloride continuously for 10 minutes, the rate being 30 drops per minute. Group 2 (31 patients, 31 eyes) received a subconjunctival injection of 0.5 ml of 0.9 % sodium chloride solution that contained 5,000 IU of RPU. For each sample, the time elapsed from the moment of RPU administration to the moment of humor sampling was noted. RPU concentration in the samples was determined by fluorescent spectrophotometry using the HITACHI 650-60 device (Japan). Results. Inforced instillations, RPU is detected in the humor of the anterior chamber starting from the 5th minute after the instillation, with rapid growth of concentration, which attains the level of 3100 IU/ml in 30 to 60 minutes. Then, however, the concentration drops, with the half-life period being 160 to 180 minutes. In subconjunctival injections RPU is detected after the same time span after the procedure; however, its concentration grows for 120 to 160 minutes, reaching the level of 2500 IU/ml, and only then begins to fall gradually, the half-life period being as long as 320-360 minutes. Conclusions. RPU may be used for the treatment of fibrinoid syndrome with practically the same efficacy by subconjunctival injections or by force instillation. This is explained by the fact that the enzyme is found in anterior chamber humor in sufficient concentrations in either case. The pharmacokinetics of therapeutic concentration of the medicine in the humor of the anterior chamber envisages a single subconjunctival administration and permits two instillations in the 24-hour period Russian ophthalmological journal. 2017; 10 (2): 18-22. (in Russian). doi: 10.21516/2072-0076-2017-10-2-18-22.