Comparative pharmacokinetic study, in the dog, of low molecular weight heparin and standard heparin by labelling with 35S
Uzan, A.; Marin, J.; Mardiguian, J.; Trillou, M.; Kiosseff, T.; Rougeot, C.
Annales Pharmaceutiques Francaises 45(6): 429-437
1987
ISSN/ISBN: 0003-4509 PMID: 2847624 Document Number: 287417
Radioactive labelling of Enoxaparin (code number PK 10169), and standard heparin, with 35S was achieved by selective N-desulfatation and resulfatation with high specific radioactivities and without any loss of biological properties. Measurements of total radioactivity, antifactor Xa activity and antifactor IIa activity were performed in dog plasma and urine after either i.v. or s.c. administration. Active fractions were separated by filtration on agarose acrylamide gels. After i.v. or s.c. injections of Enoxaparin plasma anti-Xa activities are higher than radioactive levels whereas the curves obtained with heparin are superposed. Plasma protein binding of the radioactivity is more important and persistent with Enoxaparin than with heparin. Urinary excretion of total radioactivity is quite similar with respect to be amount excreted for the two drugs, but a marked difference is observed between the composition and molecular weight to the urinary fractions. Heparin degradation occurs quickly to a large extent whereas apparently unchanged Enoxaparin is detectable in dog urine. It is suggested that the strong and persistent anti-Xa activity of Enoxaparin may be related to pharmacokinetic differences as compared with heparin, such as less metabolism and less dissociable binding to plasma proteins.