PMID: 2110870Feb 1, 1990Paper

Pharmacokinetics in chimpanzees of recombinant human tissue-type plasminogen activator produced in mouse C127 and Chinese hamster ovary cells

Chemical & Pharmaceutical Bulletin
Y TanigawaraL D Keyes

Abstract

Pharmacokinetics of recombinant tissue-type plasminogen activator (rt-PA) produced in mouse C127 cells (t-PA(C127] and Chinese hamster ovary cells (t-PA(CHO] was investigated in chimpanzees. rt-PA was administered via a constant rate i.v. infusion for 60 min, and t-PA concentration and activity in plasma were measured during and after infusion. The noncompartmental parameters were calculated according to the moment analysis method, and a population pharmacokinetic analysis was performed to obtain the mean and interindividual variability of the pharmacokinetic parameters. The mean residence time of t-PA(C127) was significantly longer and the total body clearance was significantly less than that of t-PA(CHO). t-PA(C127) has an alpha-galactosyl moiety in its carbohydrate chains, whereas such a structure is not found in t-PA(CHO). These results demonstrate that two preparations of rt-PA's with different carbohydrate structures show different pharmacokinetics, and suggest that the carbohydrate structure can affect the efficiency of hepatic uptake of t-PA. A possible mechanism is an interaction of t-PA(C127) with the natural anti-alpha-galactosyl antibody. The anti-alpha-galactosyl antibody level in plasma decreased in association wi...Continue Reading

Citations

May 1, 1994·Enzyme and Microbial Technology·N Jenkins, E M Curling
Apr 23, 2008·Current Protocols in Protein Science·D Gray, S Subramanian
Jan 1, 1995·Journal of Receptor and Signal Transduction Research·M Birnbaumer
Jan 1, 1995·Journal of Receptor and Signal Transduction Research·L Birnbaumer, M Birnbaumer
Sep 1, 1991·Progress in Cardiovascular Diseases·J HenkinH C Yang
Oct 1, 1992·Current Opinion in Biotechnology·K Furukawa, A Kobata

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