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

doi:10.1248/cpb.38.517

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 journal › Article › peer-review

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 language	English
Pages (from-to)	517-522
Number of pages	6
Journal	Chemical and Pharmaceutical Bulletin
Volume	38
Issue number	2
DOIs	https://doi.org/10.1248/cpb.38.517
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

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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

Tanigawara, Y, Hori, R, Okumura, K, Tsuji, JI, Shimizu, N, Noma, S, Suzuki, S, Erickson, MK, Couch, RC, Keyes, LD, Richards, SM & Livingston, DJ 1990, 'Pharmacokinetics in Chimpanzees of Recombinant Human Tissue-Type Plasminogen Activator Produced in Mouse C127 and Chinese Hamster Ovary Cells', Chemical and Pharmaceutical Bulletin, vol. 38, no. 2, pp. 517-522. https://doi.org/10.1248/cpb.38.517

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

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.",

keywords = "analysis, anti-a-galactosyl antibody, chimpanzee, moment, pharmacokinetics, population pharmacokinetics, recombinant tissue plasminogen activator, tissue plasminogen activator",

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

year = "1990",

doi = "10.1248/cpb.38.517",

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T1 - Pharmacokinetics in Chimpanzees of Recombinant Human Tissue-Type Plasminogen Activator Produced in Mouse C127 and Chinese Hamster Ovary Cells

AU - Tanigawara, Yusuke

AU - Hori, Ryohei

AU - Okumura, Kazuo

AU - Tsuji, Jun ichi

AU - Shimizu, Norihide

AU - Noma, Seiji

AU - Suzuki, S.

AU - Erickson, Mary K.

AU - Couch, Ronald C.

AU - Keyes, Lynne D.

AU - Richards, Susan M.

AU - Livingston, David J.

PY - 1990

Y1 - 1990

N2 - 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.

AB - 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.

KW - analysis

KW - anti-a-galactosyl antibody

KW - chimpanzee

KW - moment

KW - pharmacokinetics

KW - population pharmacokinetics

KW - recombinant tissue plasminogen activator

KW - tissue plasminogen activator

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

Abstract

Keywords

ASJC Scopus subject areas

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