Summary
Two groups of 23 and 84 patients with hip fracture received intramuscularly 100 and
300 mg dermatan sulfate (MF701) b. i. d., respectively, for the prophylaxis of deep
vein thrombosis. Median duration of treatment was 17 and 16 days, respectively. Four
blood samples were collected from each patient while under treatment. Plasma levels
of dermatan sulfate were determined by a chromogenic substrate assay. A one-compartment
model for multiple doses was employed to estimate the pharmacokinetic parameters.
Fitting was applied to mean plasma concentrations calculated for each sampling time
and weighted according to the number of samples available at each time. Thrombin clotting
time was measured on the same plasma samples. Antithrombotic efficacy was assessed
by bilateral venography.
Plasma levels of dermatan sulfate increased gradually throughout the treatment, indicating
a marked accumulation process. Time to reach steady-state was 14 or 9 days with 100
or 300 mg b. i. d., respectively. This was due to an apparent prolonged terminal half-life
(68 or 43 h), which actually reflected slow absorption from the injection sites. The
clinical efficacy of MF701 in preventing DVT was found to be dependent on the plasma
concentration of the drug and also, but less significantly, on the prolongation of
thrombin clotting time. Dermatan sulfate plasma levels greater than 9 μ/ml are advisable
to optimize efficacy in hip fracture patients.
