Electron-Beam Pegylation of Interferons to Improve Their Pharmacokinetic Properties

Drugs based on interferon α-2b are highly effective in parenteral administration. When administered per os, their effectiveness is significantly less. Electron-beam immobilization of interferons α-2b allows to improve pharmacokinetic characteristics when taking per os. In the chamber of Ussing a high rate of absorption of immobilized interferon α-2b (imINFα-2b) in the bowels up 5.46 ng/cm
²
was estimated. In vivo experiments established that imINFα-2b is actively absorbed from the lumen of the jejunum exclusively into the blood system. It was determined that imINFα-2b concentration in v. mesenterica after 1h incubation 1.5-fold higher that native form of INFα-2b. Unlike native INFα-2b, the imINFα-2b has better pharmacokinetic characteristics, so imINFα-2b almost unchanged concentration passes through the liver, and passing through the kidneys, its concentration increases to a value of 7.18±0.66 ng/L. on the basis of the pharmacokinetic parameters of imINFα-2b, such as the average retention time in the rat (MRT) - 9.98 hours; half-life (T
_1/2
) - 6.28 hours; maximum concentration (Cmax) -15.61 ng/mL; time to reach (Tmax) is 4 hours; average time of suction - 3.58 hours and clearance of 23.90 mL/HR, it can be argued that imINFα-2b is the real prototype of the oral medicines.