BIOAVAILABILITY AND PHARMACOKINETICS OF A NEW LOW-MOLECULAR-WEIGHT HEPARIN (RO-11) - A 3-WAY CROSS-OVER STUDY IN HEALTHY-VOLUNTEERS

This study reports on the bioavailability and pharmaco kinetics of a new low molecular weight heparin (RO-11), with a mean molecular weight of 3,600-3,800 daltons. It was administered to 12 healthy individuals in an open, cross-over study. Each subject was randomly assigned to three experimental treatments: a) 30 mg by subcutaneous route, b) 60 mg subcutaneously and c) 60 mg intravenously, leaving a wash-out period of one week between treatments. The pharmacokinetic profile was calculated by means of the anti-FXa effect, measured on serial samples taken before and during the 24 h period after each treatment. The effects of the drug on global coagulation tests, Antithrombin-III levels, tissue-factor pathway inhibitor activity and anti-FIIa activity were also assessed. After the intravenous injection, a maximal anti-FXa effect of 1.30 +/- 0.18 IU/ml was measured at 0.05 h and was not measurable after 12 h. After the subcutaneous injection of 30 and 60 mg, the maximal anti-FXa effect (0.34 +/- 0.08 IU/ml and 0.54 +/- 0.06 IU/ml) was reached after 2-4 h, and was not mesurable after 12-18 h. The magnitude of this effect was dose-dependent and the absorption and elimination processes followed a first-order pattern for every dose and route. RO-ll showed a biological half-life of about 5 h and a high subcutaneous bioavailability (96%).