Unfractionated Heparin and CY 216: Pharmacokinetics and Bioavailabilities of the Antifactor Xa and IIa Effects after lntravenous and Subcutaneous Injection in the Rabbit

L Briant; C Caranobe; S Saivin; P Sié; B Bayrou; G Houin; B Boneu

doi:10.1055/s-0038-1646593

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1989; 61(03): 348-353
DOI: 10.1055/s-0038-1646593

Original Article

Schattauer GmbH Stuttgart

Unfractionated Heparin and CY 216: Pharmacokinetics and Bioavailabilities of the Antifactor Xa and IIa Effects after lntravenous and Subcutaneous Injection in the Rabbit

Authors

L Briant

^*Laboratoire d’Hémostase, Centre de Transfusion, Toulouse, France
C Caranobe

^*Laboratoire d’Hémostase, Centre de Transfusion, Toulouse, France
S Saivin

^**Unité de Pharmacocinétique, Hôpital Purpan, Toulouse, France
P Sié

^*Laboratoire d’Hémostase, Centre de Transfusion, Toulouse, France
B Bayrou

^***Institut Choay, Paris, France
G Houin

^**Unité de Pharmacocinétique, Hôpital Purpan, Toulouse, France
B Boneu

^*Laboratoire d’Hémostase, Centre de Transfusion, Toulouse, France

Abstract

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Summary

This report compares the pharmacokinetics and the bioavailabilities of the antifactor Xa and of the antifactor II a activities generated by intravenous (IV) and subcutaneous (SC) injections of increasing doses of unfractionated heparin (UH) and of a low molecular weight heparin (CY 216). Rabbits were injected with 500, 1,000, 2,500 and 5,000 antifactor Xa u/kg of both heparins and their biological activities were followed at various time intervals. After IV injection the clearance of the antifactor Xa activities was independent of the dose and the clearance of UH was significantly higher than that of CY 216; after SC injection the bioavailability estimated from the antifactor Xa effect was consistently over 100% for CY 216 while that of UH increased from 27% at the lowest dose to 93% at the highest dose. The pharmacokinetic parameters estimated by the antifactor IIa activity of UH were superimposable to those calculated with the antifactor Xa activity. For CY 216 no direct comparison between the two activities was made since the dose injected expressed in antifactor IIa units was 3.4 times lower. UH and CY 216 were therefore injected intravenously to other animals at equivalent and increasing doses expressed in antifactor IIa units (50-5,000 u/kg). The pharmacokinetic parameters calculated from the curves of the antifactor IIa activities were basically identical except at the two lower doses (50 and 100 u/kg) for which UH was cleared faster than CY 216. These results indicate that the antifactor IIa activity generated by an injection of CY 216 disappears faster than the corresponding antifactor Xa activity and therefore that the antifactor Xa/antifactor IIa activity ratio of CY 216 progressively increases after SC or IV injection.

Keywords

Unfractionated heparin - Low molecular weight heparin - CY 216 - Fraxiparine^® - Pharmacokinetics

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References

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