Comparison of heparin and a semi-synthetic heparin analogue, A73025. I. Kinetics of clearance from the circulation of man following intravenous injection.

A study has been made of a low molecular weight semi-synthetic heparin analogue, A73025, that may be clinically useful as an antithrombotic agent because of its reported high specificity for antithrombin III. The clearance from the circulation of both heparin and the analogue has been studied in man following intravenous injection. Heparin obeyed almost first order kinetics when assayed using a specific anti-Xa assay and first order kinetics when measured with KCCT. At high concentrations the heparin analogue was cleared with first order kinetics when assayed both with the anti-Xa assay and with KCCT. At low concentrations the analogue produced between one half and two-thirds of the anti-Xa activity of an equal dose of heparin, producing only a small prolongation of KCCT. With increasing dose, the more specific anti-Xa potentiating effect of A73025 decreased because of a flattening of its anti-Xa dose-response curve. These results suggest that the analogue might be useful as an antithrombotic agent when it is used as a prophylactic agent.