Dialysis clearance of buflomedil in hemodialysed patients.

Buflomedil (CAS 55837-25-7, Fonzylane) is a peripherally vasoactive drug which improves nutritional blood flow in ischaemic tissue of patients with peripheral vascular disease by the way of an increase of perfusion in the microcirculation. Ten hemodialysed patients with chronic renal failure treated with intravenous infusion of 400 mg of buflomedil during 4 h of dialysis were included in the first study. This study was carried out to determine the dialysis plasma clearance and the amount of drug dialysed during the first intravenous administration of buflomedil. The dialysis clearance calculated from the amount recovered in dialysate was (mean +/- SD) 25.4 +/- 25.6 ml/min. The drug recovery resulting from hemodialysis represented a small fraction of the dose (< or = 5%). A second study was carried out to determine the accumulation of buflomedil in chronic hemodialysed patient. The drug concentration were measured before and at the end (4 h) of the infusion of buflomedil in six other patients maintained on intermittent hemodialysis (3 per week) for 4 weeks. The average Cmin and Cmax were stable during the 12 successive dialyses (mean +/- SD intervals were between 0.36 +/- 0.53 and 0.66 +/- 0.79 microgram/ml for Cmin and between 5.15 +/- 2.19 and 7.37 +/- 1.76 micrograms/ml for Cmax), showing no trend of accumulation of buflomedil. These results agree with the pharmacokinetics of the drug which is mainly metabolised in the liver and has a low renal clearance. Dialysis is unable to modify significantly the plasma concentration of the drug in regularly dialysed patients.

[Treatment of anemia in chronic hemodialysis patients with recombinant human erythropoietin: long-term results in 15 patients]. / Correction de l'anémie des hémodialysés chroniques par l'érythropoïétine recombinante humaine: résultats à long terme sur quinze malades.

Recombinant human erythropoietin (rHu-EPO) was given during 12 to 20 months in 15 long term haemodialysis anaemic (mean Hb: 6.6 +/- 1 g/dl) patients who required no blood transfusion. Patients over 65, or with severe arterial disease or with uncontrolled hypertension were not included in this trial. Correction of anaemia (mean Hb 12.1 +/- 0.6 g/dl) was achieved in all patients and maintained all along the study. An improved sense of wellbeing and increased exercise tolerance were reported by all patients. Appropriate maintenance dosage of rHu-EPO was 74 +/- 6 U/kg i.v. twice weekly. High dose oral and/or intravenous iron therapy was necessary in the absence of previous marked iron overload. One retinal venous thrombosis was the sole severe side-effect encountered. A slight but significant increase of blood pressure was observed with the need of intensifying previous anti-hypertensive therapy in one patient and of starting one in one another. Fine adjustment of the dry weight was necessary to maintain blood pressure in the normal range. Heparin requirements increased in the majority of patients because of hollow fibre clotting but there was no evidence of decreased efficacy of dialysis. In two patients clotting of arteriovenous fistula was not obviously related to the rHu-EPO treatment.

Antithrombin III and heparin cofactor II in patients with chronic renal failure undergoing regular hemodialysis.

Heparin enhances the inhibition rate of thrombin by both antithrombin III (AT III) and heparin cofactor II (HC II). We studied the activity of these two plasma proteins in patients with chronic renal failure (CRF) undergoing regular hemodialysis as their heparin requirements varied widely. In 77 normal blood donors, normal ranges (mean +/- 2 SD) were 82-122% for AT III and 65-145% for HC II. When compared with these controls 82 dialyzed CRF patients had a subnormal AT III activity and a significantly (p less than 0.001) lower HC II activity. To evaluate the effect of hemodialysis we compared AT III, HC II and total proteins in plasma before and after dialysis in 24 patients (12 with normal and 12 with low basal HC II activity). AT III and HC II activities significantly (p less than 0.001) increased in absolute value. When related to total plasma proteins, in order to suppress the influence of hemoconcentration induced by dialysis, AT III decreased significantly (p less than 0.01) whereas HC II increased slightly but significantly (p less than 0.01) in the 12 patients with low initial HC II activity. The decrease of AT III induced by heparin administrated during dialysis is likely to account for this relative decrease of AT III activity. A modification of the distribution of both HC II and heparin between the vascular wall and the circulating blood is evoked to explain the relative increase in HC II activity and the need for higher heparin dosage in patients with low HC II levels.