The pharmacokinetics of the kininogens

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

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12 Scopus citations

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

Keywords

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

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