BIOAVAILABILITY OF DESMIN, A LOW-MOLECULAR-WEIGHT DERMATAN SULFATE, AFTER SUBCUTANEOUS ADMINISTRATION TO HEALTHY-VOLUNTEERS

The bioavailability of two different s.c. doses of Desmin (a new low m olecular weight dermatan sulfate) was evaluated in 12 healthy voluntee rs (6 men, 6 women aged 22-45 years) who were injected, on 3 separate days and with a wash-out period of at least 21 days between each admin istration, with 200 and 300 mg of Desmin by the s.c. route and 200 mg by the i.v. route. Immediately before injection and at various times t hereafter (after 15 min and 30 min for i.v. only and after 1, 2, 3, 4, 6, 8, 12, and 24 h for both s.c. and i.v. dosing), blood samples were drawn to investigate bioavailability by measuring several coagulation parameters: activated partial thromboplastin time, thrombin time, inh ibition of factor Xa, Heptest, and heparin cofactor II, Furthermore th e local tolerance of the s.c. and i.v. injections were investigated. T he s.c. administration of the two Desmin doses had a negligible effect on the activated partial thromboplastin time and a very small effect on the thrombin time, measured with human thrombin; in contrast, Hepte st, heparin cofactor II, and anti-Xa activities increased, with a good drug bioavailability (more than 100%). The plasma effects of Desmin w ere dose dependent only when measured by Heptest, which also gave a gr eater response after the s.c. administrations. There were no symptoms of intolerance or pain at the injection site after single i.v. and s.c . Desmin administrations.