The antithrombotic potential of dalteparin in man assessed indirectly by Wessler's technique.

The aim of this study was to demonstrate the effectiveness of a new experimental approach for assessing the antithrombotic potential of low molecular weight heparins (LMWH) such as dalteparin. In this approach, sera obtained from healthy volunteers treated with various i.v. doses of dalteparin (30, 60 or 120 anti-Xa IU/kg) or placebo (physiological saline) were used as the thrombogenic challenge in a Wessler's stasis model of experimental venous thrombosis in the rat. Sera from placebo-treated volunteers showed a stable thrombogenic activity (0.25 ml/kg of serum producing thrombi of about 50 mg wet weight). Sera from healthy volunteers having previously received dalteparin however demonstrated dose- and time-related reductions in their thrombogenic activity. Half-lives of these effects were 300. 444 and > 480 min for 30, 60 and 120 anti-Xa IU/kg dalteparin respectively. These values were significantly higher than the corresponding anti-Xa and anti-IIa half-lives.

Postprandial lipemia, fenofibrate and coronary artery disease.

This report describes the response of patients with severe coronary artery disease to a dynamic fat load test and monitors the change induced by fenofibrate therapy. The presence of disease was associated with prolonged and exaggerated hypertriglyceridemia following the meal and with lower basal HDL cholesterol and HDL subfraction masses. A further indicator of risk was the persistence of increased amounts of retinyl palmitate in the plasma of severely affected individuals 24 h after its ingestion with the meal. These observations are consistent with the proposal that the clearance of chylomicrons and their remnants is impaired in coronary atherosclerosis. Fenofibrate reduced alimentary lipemia following the fat load in both normo- and hypercholesterolemic subjects. This was associated with a 10% rise in plasma HDL cholesterol levels. The improvement in chylomicron catabolism probably derived from a 37% increase (P less than 0.001) in lipoprotein lipase activity induced by fenofibrate. Hepatic lipase on the other had was only slightly affected by treatment.

With whom does the French drug industry want to work for phase I?

Industry chooses phase I partners by evaluating quality versus cost. However, since December 20, 1988, in France only those centers, private or public, authorized by the French authorities can be chosen. However, ability to perform rapidly, reliability and worldwide acceptability of results will be considered in choosing the phase I partner.

[Writing the clinical trial report]. / La rédaction du rapport d'un essai clinique.

The clinical study report is a key document, representing as it does one of the elements of the drug registration file. The authors propose here a general design for a controlled trial which offers the advantage of a methodical approach covering most clinical study situations.

[Pharmacoclinical comparison of 2 dosage forms of trihexyphenidyl]. / Comparaison pharmacoclinique de deux formes galéniques de trihexyphénidyle.

The peak plasma level of Trihexyphenidyl sustained release from (THR = Parkinane sustained release) is lower than that produced by the simple form (THS = Artane) while it provides a quantitatively equivalent serum concentration. The less noticeable with sustained release Trihexyphenidyl. THR plasma levels, maintained relatively constant by a progressive release of the active principle, are sustained over a 24-hour period, allowing a simplified mode of administration: the drug may be given once a day.

[Comparative pharmacological activity of triamcinolone acetonide and of a new topical steroid: amcinonide, after percutaneous or oral administration (author's transl)]. / Comparaison des effets pharmacologiques de l'acétonide de triamcinolone et d'un nouveu dermocorticoide: l'amcinonide après application par voie percutanée ou administration par voie orale.

This study was carried out in order to compare the potential anti-inflammatory activity and the level of action of triamcinolone acetonide (Triam. Ac.) and amcinonide (Amc.) after percutaneous administration to animals. Administered per os to rats Amc. is 18 times less active (DI50 1,85 mg . kg-1) on carrageenin plantar edema and 10 times less active (DI50 4,2 mg . kg-1) than Triam Ac. on air pouch granuloma with carrageenin. The potential anti-inflammatory activity at the various levels of tissues under the skin was evaluated with an ointment and a cream containing the two corticosteroïds through three methods: --vasoconstrictor assays on guinea pig showing cutaneous activity; --plantar edema showing subcutaneous activity; --air pouch granuloma showing anti-exsudative activity. The results are as it follows: --vasoconstrictor activity Amc. higher than Triam. Ac.; --plantar edema Amc. equal to Triam Ac.; --air pouch granuloma Am. lesser than Triam. Ac. The two corticoids administered percutaneously show any thymolytic activity on young female rats. Though Amc. is far less active than Triam. Ac. when orally administered, nevertheless it is a powerful dermocorticoïd with a poor systemic activity. Its local effects are less profound than those of Triam. Ac.