Increasing the plasma half-life of trichosanthin by coupling to dextran.

摘要: Abstract Trichosanthin (TCS) is a plant protein which has wide spectrum of pharmacological activities. It was demonstrated recently that this compound suppressed the replication human immunodeficiency virus (HIV-1) in vitro. The mechanism action believed to be inhibition synthesis. low molecular weight expected easily filtered and eliminated through kidney. To minimize renal loss, size trichosanthin can increased by coupling dextran. larger complex will not undergo glomerular filtration therefore loss prevented. This study investigates kidney's role elimination beneficial effect afforded dextran prolonging plasma half-life. For purpose, radioimmunoassay been developed determine concentration TCS urine. sensitivity assay nanogram range. coupled T40 dialdehyde method successful confirmed gel chromatography. retained specific binding antibodies with decreased affinity partially reversed after incubation dextranase; an enzyme digested pharmacokinetics intravenously administered (0.75 mg/kg) compared between two groups rats normal impaired function (bilateral arterial ligation). Rats ligation showed decrease clearance from 4780 ± 570 220 20 smL/min increase mean residence time 9 1 145 16 min. Despite several-fold difference these parameters, recovery rat urine only 0.38 0.05%. value using higher injection doses. data indicate kidney important organ for trichosanthin. When dextran-trichosanthin injected into activity detected All pharmacokinetic parameters suggest dextrantrichosanthin stayed longer body maintained much than