Roussel Uclaf

About: Roussel Uclaf is a based out in . It is known for research contribution in the topics: Alkyl & Alkoxy group. The organization has 1888 authors who have published 2338 publications receiving 36508 citations.

Trandolapril: pharmacokinetics of single oral doses in healthy male volunteers

Abstract: The pharmacokinetics and dose proportionality of trandolapril, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated in 12 healthy male volunteers in a four-way randomized crossover study over the therapeutic dose range, 0.5-4 mg. Trandolapril is rapidly absorbed, with a single elimination half-life (t1/2) of 0.72 h, irrespective of dose. Peak plasma levels (Cmax) occurred at 0.5 h and were proportional to the dose, as was the area under the plasma concentration-time curve (AUC). Concentration of the active metabolite (trandolaprilat) increased with increasing doses but in a nonlinear fashion, probably owing to saturable plasma ACE binding. However, the Cmax and AUC values for trandolaprilat were directly proportional to the highest doses, 2 and 4 mg, suggesting linear kinetics for the trandolaprilat, which is not bound to ACE. Trandolapril showed linear kinetics but trandolaprilat showed some features of nonlinear kinetics, particularly at low doses.

Sandwich-type enzyme immunoassay for big endothelin-1 in plasma: concentrations in healthy human subjects unaffected by sex or posture

Abstract: A sandwich-type enzyme immunoassay has been developed for measuring human big endothelin-1 (big ET-1) in human plasma and supernatant fluids from human cell cultures. Big ET-1 is the precursor of endothelin 1 (ET-1), the most potent vasoconstrictor known. A rabbit antibody raised against the big ET-1 COOH-terminus fragment was used as an immobilized antibody (anti-P16). The Fab' fragment of a monoclonal antibody (1B3) raised against the ET-1 loop fragment was used as the enzyme-labeled antibody, after being coupled to acetylcholinesterase. The lowest detectable value in the assay was 1.2 pg/mL (0.12 pg/well). The assay was highly specific for big ET-1, demonstrating no cross-reactivity with ET-1, <0.4% cross-reactivity with big endothelin-2 (big ET-2), and <0.1% with big endothelin-3 (big ET-3). We used this assay to evaluate the effect of two different postural positions (supine and standing) on plasma big ET-1 concentrations in 11 male and 11 female healthy subjects. Data analysis revealed that neither sex nor body position influenced plasma big ET-1 concentrations. This assay should thus permit the detection of possible variations in plasma concentrations of big ET-1 in certain pathologies and, in association with ET-1 assay, make possible in vitro study of endothelin-converting enzyme activity in cell models. Such studies could clarify the physiological and clinical roles of this family of peptides.

Antagonism of scopolamine-induced memory impairments in rats by the muscarinic agonist RU 35 926 (CI-979)

Abstract: The promnesic effects of RU 35 926 (CI-979), a muscarinic receptor agonist, were evaluated on memory impairments induced by the muscarinic antagonist scopolamine, using a radial arm maze task, in comparison with tetrahydroaminoacridine (THA), a cholinesterase inhibitor. Groups of rats were trained in a standard version of the radial maze until they had attained an asymptotic level of performance. The animals were then retested with one trial a day. Twenty minutes before each retest, the rats were given subcutaneous administration of 0.1 mg/kg scopolamine. Oral administration of RU 35 926 (0.02, 0.05, 0.1, 0.2, and 0.5 mg/kg) 30 min before memory retest markedly reduced or suppressed the scopolamine-induced deficit. This reduction was evidenced by a significant decrease in the different types of errors and an increase in the number of correct responses. THA (3 mg/kg, intraperitoneally or orally) given 20 min to testing also significantly reduced or suppressed the scopolamine-induced deficits. These results show that RU 35 926 possesses the capacity to reduce memory impairments induced by a deficit of cholinergic transmission in the rat.