The pharmacokinetics of the kininogens

Alvin H. Schmaier, Richard Wahl, Susan J. Fisher, Dean Brenner

Research output: Contribution to journalArticle

Abstract

Recent evidence has shown that plasma high molecular weight kininogen and both kininogens have the ability to modulate prekallikrein activation and thrombin-induced platelet activation, respectively. However, nothing is known about the plasma clearance and tissue distribution of these proteins. We examined the in vivo pharmacokinetics of high (HK) and low (LK) molecular weight kininogens in rats. 125I-HK and -LK molecular weight kininogens' clearance in rats best-fitted a biexponential model. For HK, the t(1/2)α and t(1/2)β were 0.6 and 9.5 h and for LK, 0.78 and 7.4 h, respectively. 125I-kinin-free HK (cleaved HK) was cleared with a t(1/2)α and t(1/2)β of 0.45 and 9.9 h, respectively. 125I-Domain 3 of kininogens was cleared with a t(1/2)β and t(1/2)c of 0.99 and 13.3 h, respectively. HK was mostly concentrated in lung; LK, domain 3, and cleaved HK were mostly concentrated in kidney. The kininogens were also concentrated in liver, spleen, and skin. These studies indicate that protein size rather than form is the major determinant of its clearance. Furthermore, the distribution of the kininogens is where bradykinin metabolism and activity are well described.

Original languageEnglish (US)
Pages (from-to)293-297
Number of pages5
JournalThrombosis Research
Volume92
Issue number6
DOIs
StatePublished - Dec 15 1998
Externally publishedYes

Fingerprint

Kininogens
Pharmacokinetics
Low Molecular Weight Kininogens
High Molecular Weight Kininogens
Prekallikrein
Kinins
Platelet Activation
Bradykinin
Tissue Distribution
Thrombin
Proteins
Spleen
Molecular Weight
Kidney
Lung
Skin
Liver

Keywords

  • D3 Domain
  • High molecular weight kininogen
  • Kinin-free kininogen
  • Low molecular weight kininogen
  • Pharmacokinetics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Hematology

Cite this

Schmaier, A. H., Wahl, R., Fisher, S. J., & Brenner, D. (1998). The pharmacokinetics of the kininogens. Thrombosis Research, 92(6), 293-297. https://doi.org/10.1016/S0049-3848(98)00142-X

The pharmacokinetics of the kininogens. / Schmaier, Alvin H.; Wahl, Richard; Fisher, Susan J.; Brenner, Dean.

In: Thrombosis Research, Vol. 92, No. 6, 15.12.1998, p. 293-297.

Research output: Contribution to journalArticle

Schmaier, AH, Wahl, R, Fisher, SJ & Brenner, D 1998, 'The pharmacokinetics of the kininogens', Thrombosis Research, vol. 92, no. 6, pp. 293-297. https://doi.org/10.1016/S0049-3848(98)00142-X
Schmaier AH, Wahl R, Fisher SJ, Brenner D. The pharmacokinetics of the kininogens. Thrombosis Research. 1998 Dec 15;92(6):293-297. https://doi.org/10.1016/S0049-3848(98)00142-X
Schmaier, Alvin H. ; Wahl, Richard ; Fisher, Susan J. ; Brenner, Dean. / The pharmacokinetics of the kininogens. In: Thrombosis Research. 1998 ; Vol. 92, No. 6. pp. 293-297.
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