Pharmacokinetics in Chimpanzees of Recombinant Human Tissue-Type Plasminogen Activator Produced in Mouse C127 and Chinese Hamster Ovary Cells

Yusuke Tanigawara, Ryohei Hori, Kazuo Okumura, Jun ichi Tsuji, Norihide Shimizu, Seiji Noma, S. Suzuki, Mary K. Erickson, Ronald C. Couch, Lynne D. Keyes, Susan M. Richards, David J. Livingston

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 a-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-a-galactosyl antibody. The anti-a-galactosyl antibody level in plasma decreased in association with the plasma levels of t-PA(C127) but was unaffected by t-PA(CHO) levels.

Original languageEnglish
Pages (from-to)517-522
Number of pages6
JournalChemical and Pharmaceutical Bulletin
Volume38
Issue number2
DOIs
Publication statusPublished - 1990 Jan 1
Externally publishedYes

Keywords

  • analysis
  • anti-a-galactosyl antibody
  • chimpanzee
  • moment
  • pharmacokinetics
  • population pharmacokinetics
  • recombinant tissue plasminogen activator
  • tissue plasminogen activator

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

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  • Cite this

    Tanigawara, Y., Hori, R., Okumura, K., Tsuji, J. I., Shimizu, N., Noma, S., Suzuki, S., Erickson, M. K., Couch, R. C., Keyes, L. D., Richards, S. M., & Livingston, D. J. (1990). Pharmacokinetics in Chimpanzees of Recombinant Human Tissue-Type Plasminogen Activator Produced in Mouse C127 and Chinese Hamster Ovary Cells. Chemical and Pharmaceutical Bulletin, 38(2), 517-522. https://doi.org/10.1248/cpb.38.517