N' alkylamine low molecular mass heparins (LMM-heparin-tyramine and LMM-heparin-tyramine-fitc) exhibit long lasting anticoagulant effects.
The pharmacodynamic and pharmacokinetic properties of endpoint-attached N'alkylamine derivatives of low molecular mass heparin (LMMH), low molecular mass heparin (LMMH), low molecular mass heparin-tyramine (LMMH-tyr) and low molecular mass heparin-tyramine-fluorescein-5-isothiocyanate (LMMH-tyr-fitc) were investigated ex vivo. After intravenous bolus injection of LMMH, LMMH-tyr and LMMH-tyr-fitc (150 aXa U/kg) to Sprague-Dawley rats (n = 8), LMMH-tyr and LMMH-tyr-fitc displayed decreased clearances. The beta-half-life time of the antifactor Xa (aXa) of "endpoint-attached heparins" was significantly prolonged: LMMH-tyr (125 min), LMMH-tyr-fitc (141 min) compared to LMMH (69 min). The pharmacokinetics of LMMH-tyr-fitc were measured with reversed phase high performance liquid chromatography (RP-HPLC). It showed a decreased clearance and a prolonged half-life time (132 min). The selectively tagged LMMH-tyramine and LMMH-tyramine-fitc may be used to investigate the pharmacokinetics, plasma protein and cellular binding of low molecular mass heparins.
Malsch
R
R
First Department of Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany.
Piazolo
L
L
Harenberg
J
J
Heene
D L
DL
D000818:Animals; D000925:Anticoagulants / Q000493:pharmacokinetics / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology; D001779:Blood Coagulation Factors / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006495:Heparin, Low-Molecular-Weight / Q000493:pharmacokinetics / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000925:Anticoagulants; D001779:Blood Coagulation Factors; D006495:Heparin, Low-Molecular-Weight