Study On Pharmacokinetics Of Recombinant Human IFN-ω Modified With PEG

The thesis focuses on the development of PEG-rhIFN-ω, discusses the pharmacokinetics and concentration distribution in different tissues of PEG-rhIFN-ω. The essay is to master transformational rules of PEG-rhIFN-ω, and finally to provide important pharmacokinetics parameter for safe clinic drug using and for supplying bases and reference of proper using drug.Mice are used in the experiments with injection of rhIFN-ωand PEG-rhIFN-ω. This essay discusses that polyethyleneglycol modification can influence pharmacokinetics parameter of rhIFN-ωin the approach of Double antibody sandwich method, and from the aspect of blood concentration-time relation, and from the aspect of concentration distribution in different tissues.. The primary conclusions are the following.①Research of rhIFN-ωantibody and rhIFN-ωantibody marked with horseradish peroxidase (HRP), study on their formation, establishment of detected methods of rhIFN-ω's concentration in blood and distribution in different tissues by Double antibody sandwich ELISA.②Measure the different time's blood concentration-time curve after the injection of rhIFN-ωand PEG-rhIFN-ωof three doses (5μg/kg, 3μg/kg, and 1μg/kg) into mice. Apply method of compartment model to the pharmacokinetics parameter estimation of rhIFN-ωand PEG-rhIFN-ω. And the results show that blood concentration-time curves of rhIFN-ωand PEG-rhIFN-ωare fitted to a two-compartment model. The t1/2βof rhIFN-ωis 0.866±0.18h, PEG-rhIFN-ωis 2.86±0.27h, which is three times of rhIFN-ω. The clearance (CL) is 0.416mL/h·kg , PEG-rhIFN-ωis 0.492mL/h·kg. The volume of distribution (Vd) of rhIFN-ωis estimated to be 9.81L/kg, PEG-rhIFN-ωis 11.80L/kg. The results show polyethyleneglycol modification can obviously prolong interferon-ω's half-life period (t1/2).③By using enzyme linked immunosorbent assay methods, detect concentration distribution in heart, liver, kidney, spleen, bladder and stomach after the interjection of PEG-rhIFN-ω5μg/kg into mice. The outcomes show that polyethyleneglycol's modification can distinctively heighten interferon omega's utilizing rate in different tissues, and with strong tissues pertinence. The results show that PEG-rhIFN-ωspreads higher than rhIFN-ωexcept in kidney, polyethyleneglycol modification can improve the using rate of rhIFN-ωin different tissues.