Evolution of atenolol kinetics when hypothyroidism is corrected

Summary A single oral dose of atenolol 100 mg was given to 7 hypothyroid patients (4 F, 3 M), before and after correction of hypothyroidism, mean delay 3.5 months (2 to 6.5 months).There was no change in the elimination parameters of atenolol, but the maximal plasma atenolol concentration was increased (1.66 to 7.37 mg·l^–1) as was the AUC (14.9 to 52.1 mg·l^–1·h) when the hypothyroidism had been treated. Only one patient differed: he had had a supra-selective vagotomy, and had similar curves before and after treatment of the hypothyroidism, both being similar to the plasma concentration curves found in the other patients after correction of the hypothyroidism.The results suggest an increase in the bioavailability of atenolol when hypothyroidism is corrected. The findings in the patient with vagotomy suggest that the decreased bioavailability during hypothyroidism might be related to changes in intestinal pH. Further studies are needed of the impact of hypothyroidism on gastric and pancreatic or biliary function and its consequences for drug absorption, and drug pharmacokinetics.     

Improvement of diabetic polyneuritis with naftidrofuryl. Preliminary results

This study was a 6-month open trial of the effects of naftidrofuryl fumarate (600 mg/day orally) on the clinical and electrophysiological signs of diabetic polyneuropathy in 15 patients. A scored clinical evaluation and an indexed electrophysiological examination were done at inclusion, and after 3 and 6 months. Mean clinical score and electrophysiological index was improved after 3 months of therapy, the improvement persisting at 6 months, with no change in control of diabetes. These results could be related to the vasodilating properties of the drug, causing an increase in nerve temperature, or to a specific neurotropic action, as recently demonstrated in rats. Controlled studies are necessary to confirm these results, and explore the mechanism of this improvement.     

Renal function and histologic studies in rats treated by floctafenin (author's transl)]

The nephrotoxic action of floctafenin has been studied in rats. When administered orally at 20 or 50 mg/kg/day for 20 or 50 days, this analgesic agent had no effect on the renal function, either in intact rats or in animal with reduced renal parenchyma. There is no histological change in the kidneys of the treated animals except some focal dilatations of the distal tubules. The tubular alterations were more important in treated and untreated rats with nephronic reduction. The whole body autoradiographic studies of rats treated with 14C floctafenin showed that liver and kidney accumulate radioactivity, and that the intake of radiolabeled compounds is twice higher in renal cortex than in medulla. This study suggests that the toxicity of floctafenin for the rat kidney is very low or none.     

Is citrate theophylline adenosine dipyridamole (CTAD) better than citrate to survey unfractionated heparin treatment? Has delayed centrifugation a real impact on this survey?

Journal of Thrombosis and Thrombolysis - Unfractionated heparin (UFH) is the main anticoagulant used in intensive care unit. The anticoagulant effect is monitored by activated partial thrombin time...     

Thrombin generation profile in non-thrombotic factor V Leiden carriers

Journal of Thrombosis and Thrombolysis - Factor V Leiden (FVL) mutation is the most common genetic risk factor for venous thromboembolism. In families with a history of thrombosis, FVL can be...     

Protein binding of digitoxin,valproate and phenytoin in sera from diabetics

Summary Chronic hyperglycaemia results in glycation of serum albumin and might affect the binding of drugs. The aim of the present study was to compare, using an equilibrium dialysis method, the protein binding of therapeutic concentrations digitoxin, valproate and phenytoin in sera from 70 insulin-dependent diabetics and 25 controls. Drug concentrations were measured by fluorescence immunopolarisation. Glycated albumin was measured by laser nephelometry after affinity chromatography.In sera from diabetics, protein binding of digitoxin (88.8 versus 89.9%) was unchanged; the protein binding of valproate (75.2 versus 80.7%) and phenytoin (67.9 versus 75.3%) was significantly decreased, but with no correlation with the concentration of glycated albumin.We conclude that the difference in protein binding between diabetic and control sera is due to glucose-independent modification of albumin in diabetics.