Pharmacology of desmin (low molecular weight dermatan sulphate) in healthy volunteers following intravenous bolus administration of different dosages (200, 400, 800 mg).
Eight healthy volunteers (6 males, 2 females, mean age 31.6 yrs), were administered--on three separate days--200, 400 and 800 mg of a new low molecular weight Dermatan sulphate (Desmin), given as a single i.v. bolus (2 min.) injection. Before each administration and 10, 20, 30 min., 1, 2, 4, 8, 12, 24 hours after, blood samples were drawn and the following coagulative assays performed: aPTT (activated Partial Thromboplastin Time), TT (Thrombin Time), anti Xa (Xa Factor inhibition), Heptest, Stachrom D.S.. Furthermore, a kinetic analysis was performed on the activity curves calculated on the Heptest and Stachrom data. Plasma peak values and half lives of the parameters checked showed a clear dose-effect relationship. aPTT and TT showed very short-lasting variations and the inhibition of Factor Xa was moderate, but significant. The most evident and specific effects of Desmin were those on Heptest and Stachrom D.S.: both tests were influenced in a clear-cut and dose-dependent way, mainly as a consequence of the action of Desmin on HCII, with partially different kinetic patterns. A series of in vitro experiments proved an anti Xa effect of Desmin, mediated by antithrombin III, well above the possible interference of the small (< 1%) heparin contaminants in Desmin. An even more marked anti Xa activity was seen in the in vivo study, an observation so far unrecognized for this type of drug: some possible interpretations of this fact are discussed.
Dettori
A G
AG
Centre for Haemostatic Diseases, Maggiore Hospital, Parma, Italy.
Milani
M R
MR
Manotti
C
C
Zamboni
V
V
Palazzini
E
E
Barbanti
M
M
D000328:Adult; D000991:Antithrombins / Q000493:pharmacokinetics / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D003893:Desmin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male
D000991:Antithrombins; D003893:Desmin; D065427:Factor Xa Inhibitors