Disease relevance of Etintidine

• Based on the high degree of specificity for the H2-receptor and its potent gastric antisecretory activity, etintidine may prove to be a useful agent in the treatment of peptic ulcer disease [1].
• Clinical pharmacology of etintidine in patients with duodenal ulcer [2].

High impact information on Etintidine

• Low affinities for histamine H1 (pA2 = 4.2), cholinergic (pA2 = 4.4) and beta adrenergic (pA2 = 3.8) receptors indicated that etintidine has a high degree of specificity for the H2-receptor [1].
• The metabolic fate of etintidine, a new H2-receptor antagonist, was studied in the rat, dog, and human [3].
• In conclusion, etintidine may cause mainly the same drug interactions as cimetidine but seems to be a more potent inhibitor [4].
• This method has been used for the determination of plasma etintidine levels in humans and mice after oral administration of etintidine and was found to be suitable for pharmacokinetic/bioavailability studies of etintidine in humans and animals [5].
• (1) Etintidine did not show any chromosome aberrations in the presence or absence of S9 mix at any concentration tested [6].

Biological context of Etintidine

• From type II spectral changes follows that the affinity of rat liver microsomal preparations for etintidine is about 5 times as high as for cimetidine when comparing both high and low affinity binding sites [4].
• (2) Etintidine did not increase the frequency of micronuclei in polychromatic erythrocytes even at the dose of 50% of the LD50 at single (24 h) and chronological preparation after drug administration [6].
• Single-dose and multiple-dose pharmacokinetics of etintidine in healthy volunteers [7].
• Cimetidine and etintidine were comparatively weak, competitive inhibitors of TMQ metabolism (IC50 greater than 300 microM) and clonidine and cibenzoline were even less inhibitory (IC50 greater than 1 mM) [8].
• Symmetrical 95% confidence interval analyses showed that the observed decreases of less than 11% in the AUC values of etintidine following the concomitant administration of food or milk were within 17% of the fasting value and, therefore, may not be of clinical significance [9].

Anatomical context of Etintidine

• On the sulphoxidation of cimetidine and etintidine by rat and human liver microsomes [10].
• We analyzed sigmoid-shaped concentration-response curves to both agents; the concentrations causing 50% inhibition of meal-stimulated gastric acid secretion were 0.44 +/- 0.04 and 0.15 +/- 0.04 micrograms/ml for cimetidine and etintidine, respectively [2].
• Additional pharmacological and biochemical studies indicate that etintidine displays minimal competition with appropriate ligands for the alpha 1, alpha 2, cholinergic and neuroleptic receptors in vitro, and has minimal effects on the immunological, autonomic and central nervous systems at doses much higher than antisecretory doses [11].
• Both cimetidine and etintidine inhibited the binding of [3H]-cimetidine to plasma membranes, in a dose-dependent manner, with an IC50 of 1.70 X 10(-6) M and 0.51 X 10(-6) M, respectively [12].
• In the 4 hr pylorus-ligated rat etintidine is a potent inhibitor of total acid output (ED50 = 22 mg/kg, i.d.), total pepsin output, and is well absorbed from the gastrointestinal tract [11].

Associations of Etintidine with other chemical compounds

• The order of potency as histamine H2-receptor and gastric antisecretory antagonists was cimetidine less than etintidine less than ranitidine less than tiotidine [1].
• The mutagenic effects of etintidine (BL-5641), a novel histamine H2-receptor antagonist, was assessed using the chromosome aberration test in CHL cells and the micronucleus test in mice [6].
• Statistical evaluation of the pharmacokinetic parameters of 4-hydroxypropranolol indicates that etintidine also increased the AUC0-24 values (43.8 vs. 16.4 ng.hr/ml, p = 0.0028) and prolonged the elimination half-life (4.87 vs. 1.97 hr) of 4-hydroxypropranolol [13].
• Theophylline was rapidly absorbed following oral administration of the theophylline elixir to both the placebo and etintidine treatment groups [14].
• Comparison of the pharmacokinetic parameters of propranolol between etintidine and the placebo groups indicates that etintidine significantly increased the AUC0-infinity values (573.5 vs. 146.4 ng.hr/ml, p = 0.0001) and prolonged the elimination half-life (4.61 vs. 2.33 hr) of propranolol [13].

Gene context of Etintidine

• Characterization of the solution degradation products of etintidine, an H2-receptor antagonist [15].
• While high doses of both cimetidine and etintidine increase serum prolactin levels in rats, the effect of etintidine is less than that of cimetidine [11].

Analytical, diagnostic and therapeutic context of Etintidine

• Blood samples were collected prior to and at various times after each treatment and plasma levels of etintidine were determined by high performance liquid chromatography [9].
• A three-way crossover study was conducted in 24 normal, male volunteers to compare the bioavailability of etintidine from capsules (2 X 200 mg) taken under fasting conditions, with food and with milk [9].

References