THE PHARMACOKINETICS OF ¹²⁵-I DERMATAN SULFATE IN THE RABBIT

We have determined the main pharmacokinetic parameters of dermatan sulfate (DS), a catalyst of IIa-heparin cofactor II (HC II) interaction which presents antithrombotic properties in the rabbit. DS (Pharmuka, France) was conjugated with SHPP and iodinated using the chloramine T method. The labelled derivative had the same MW distribution and biological activities than.the native one. Rabbits were injected by 5 ucies of ¹²⁵I-DS (0.6 ug) and increasing doses of unlabelled DS. Serial blood samples were collected to measure cpm disappearance and, in some cases, residual biological activity was determined (ex vivo quantitation of IIa- ¹²⁵I-HC II complexes). The cpm curves were broken into 3 exponentials : alpha, beta and gamma. The beta exponential was closely superimposable to the curves of biological activity disappearance. The main pharmacokinetic parameters are indicated in the Table (mean ± SD) : there was a slight (non-significant) tendency to the half life (Tl/2) prolongation and to the reduction of both the clearance (cl) and the volume of distribution (Vd). Thus after IV injection, the pharmacokinetics of DS mimics that of LMW-heparin in the rabbit : Tl/2 is in the same order of magnitude and independent of the dose delivered. These results are promising for the future development of this compound as an antithrombotic agent.