Effects of plasma lipid levels on blood distribution and pharmacokinetics of cyclosporin A.

The present study attempted to characterize the distribution of cyclosporin A (CsA) among the lipoprotein fractions, very-low-, intermediate-, low-, and high-density (VLDL, IDL, LDL, and HDL, respectively) in the plasma of patients awaiting heart transplantation and the influence of plasma lipid constituents on the pharmacokinetics of CsA. Major fractions of a therapeutic concentration of CsA were found in HDL and in LDL. In addition, plasma lipid concentrations (total cholesterol, triglycerides, phospholipids, VLDL-cholesterol--TC, TG, PL, VLDLc, respectively) are positively correlated with the CsA distribution within the LDL fraction, and negatively correlated with the CsA distribution within the HDL fraction. Thus, the percentage of CsA in each type of lipoproteins was shown to vary with the lipid levels among individuals. A significant negative correlation was found between apparent distribution volume at steady state (Vss) in plasma and TC, PL, and LDLc and between the area under the curve measured in blood (AUCB) for whole blood and PL.

[Value of a fraction of low molecular weight heparin, enoxaparine, in patients at high risk of hemorrhage and thrombosis]. / Intérêt d'une fraction d'héparine de bas poids moléculaire, l'énoxaparine, chez des patients à hauts risques hémorragique et thrombotique.

Treatment of patients with both thromboembolic manifestations and acute bleeding episodes is poorly defined. The use of low molecular weight heparin fractions has been shown to provide prophylactic antithrombotic activity in humans, with the possibility of fewer hemorrhagic complications because of their low anticoagulant activity and weaker action on platelets. An open trial was carried out in 50 patients. 47 of whom had a recent history of thromboembolic accident (34 venous thrombosis, including 13 with pulmonary embolism, 9 systemic arterial episodes, 4 cardiac emboli) and 3 who required prophylaxis. Conventional heparin therapy was contraindicated in all patients: 30 because of major digestive or muscle hemorrhage and 20 with high hemorrhagic risk (neurosurgery, deep thrombocytopenia). Enoxaparine (Laboratoire Pharmuka, Gennevilliers) was administered as 1 mg/kg/24 hours as 2 divided injections with adjustment to maintain an anti-Xa activity of 0.1 to 0.4 IU/ml. Antithrombotic efficacy as function of type of pathology was rated excellent in all patients, while tolerance, evaluated similarly by tests chosen as a function of type of hemorrhage, was good: one patient had moderate bleeding after accidental overdose and 4 patients minor bleeding. Enoxaparine by subcutaneous injection could represent a new therapeutic approach by improving the efficacy/risk ratio in this type of patients.