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 language | English |
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Pages (from-to) | 517-522 |
Number of pages | 6 |
Journal | Chemical and Pharmaceutical Bulletin |
Volume | 38 |
Issue number | 2 |
DOIs | |
Publication status | Published - 1990 |
Externally published | Yes |
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