Absence Of Ranitidine Research Articles

Interaction of palmitic Acid with metoprolol succinate at the binding sites of bovine serum albumin.

The aim of this study was to characterize the binding profile as well as to notify the interaction of palmitic acid with metoprolol succinate at its binding site on albumin. The binding of metoprolol succinate to bovine serum albumin (BSA) was studied by equilibrium dialysis method (ED) at 27°C and pH 7.4, in order to have an insight in the binding chemistry of the drug to BSA in presence and absence of palmitic acid. The study was carried out using ranitidine as site-1 and diazepam as site-2 specific probe. Different analysis of binding of metoprolol succinate to bovine serum albumin suggested two sets of association constants: high affinity association constant (k1 = 11.0 x 10(5) M(-1)) with low capacity (n1 = 2) and low affinity association (k2 = 4.0×10(5) M(-1)) constant with high capacity (n2 = 8) at pH 7.4 and 27°C. During concurrent administration of palmitic acid and metoprolol succinate in presence or absence of ranitidine or diazepam, it was found that palmitic acid displaced metoprolol succinate from its binding site on BSA resulting reduced binding of metoprolol succinate to BSA. The increment in free fraction of metoprolol succinate was from 26.27% to 55.08% upon the addition of increased concentration of palmitic acid at a concentration of 0×10(-5) M to 16×10(-5) M. In presence of ranitidine and diazepam, palmitic acid further increases the free fraction of metoprolol succinate from 33.05% to 66.95% and 40.68% to 72.88%, respectively. This data provided the evidence of interaction at higher concentration of palmitic acid at the binding sites on BSA, which might change the pharmacokinetic properties of metoprolol succinate.

Influence of nitric oxide agents in the dorsal hippocampus of mice on anxiogenic-like effect induced by histamine

Histaminergic receptors and neuronal nitric oxide synthase (nNOS) are co-expressed at high levels in the hippocampal neurons and alter anxiety-like behaviors in rodents. Since the dorsal hippocampus may be involved in modulation of anxiety-like behaviors, the aim of the present study was to assess whether the nitric oxide (NO) system in the dorsal hippocampus affects anxiety-like behaviors induced by histaminergic agents in mice. The effects of the NO precursor, L-arginine and NOS inhibitor, L-nitro-amino-methyl-ester (L-NAME) on histamine, pyrilamine and ranitidine responses in elevated plus maze (E.P.M.) in mice were investigated. Intra-CA1 microinjection of histamine (9μg/mouse) or H1 receptor antagonist, pyrilamine (3, 6 and 9μg/mouse), but not H2 receptor antagonist, ranitidine decreased the percentage of open arm time (%OAT) and open arm entries (%OAE), without affecting locomotor activity, suggesting an anxiogenic-like response. Both L-arginine (0.4 and 0.8μg/mouse) and L-NAME (40ng/mouse) when injected into the dorsal hippocampus induced anxiety-like behaviors, but the drugs reversed the anxiogenic response induced by the effective dose of histamine (9μg/mouse) or pyrilamine (9μg/mouse). Our results also indicated that intra-CA1 administration of L-arginine and L-NAME, in the presence or absence of ranitidine, exerted an anxiogenic effect. The results may indicate a modulatory role for NO in the dorsal hippocampus in the anxiogenic-like response induced by histamine or pyrilamine.

Inhibition of gastric acid secretion by Ya-hom in isolated mouse whole stomach

Background: Ya-hom, the traditional Thai formula for abdominal discomfort treatment has, been reported to inhibit gastric acid secretion in gastric fistula rats. However, the mechanism underlying its action remains unclear. Objective: To investigate the gastric acid inhibitory action of Ya-hom and its mechanism of action by using an isolated mouse whole stomach model. Methods: The gastric acid secretion of isolated mouse whole stomach was stimulated by histamine (5.0 μM) or bethanechol (10 or 100 μM) after adding the inhibitors (atropine 1 μM, ranitidine 10 μM, indomethacin 0.1 μM or L-NAME 300 μM) and/or Ya-hom to the serosal solution. The effluent perfusate was collected continuously in 10-minute fractions for 120 minutes after stimulation. Results: Re-dissolved lyophilized Ya-hom extract at doses of 2.5, 5.0, 10.0, and 20.0 mg/mL inhibited histaminestimulated gastric acid secretion in a dose-dependent manner. Inhibition of Ya-hom (10 mg/mL) was also observed in the presence of atropine (1 μM), which was used to eliminate effects of endogenous acetylcholine. Ya-hom inhibited bethanechol-stimulated gastric acid secretion in the presence and absence of ranitidine. While the inhibitory action of Ya-hom on histamine-stimulated gastric secretion was not affected by indomethacin, it was attenuated by concomitant treatment with the nitric oxide synthase inhibitor (L-NAME). Conclusion: Ya-hom did not stimulate gastric acid secretion in the isolated mouse whole stomach. Ya-hom significantly inhibited gastric acid secretion after this was stimulated via histamine or bethanechol. Nitric oxide stimulation plays an important role in the inhibitory action of Ya-hom.

Ethanol Pharmacodynamics at Low Blood Concentrations.

Ranitidine has been shown to produce increases in blood alcohol concentration (BAC) after low doses of alcohol. The objective of this study was to reproduce, in a controlled setting, the BACs seen after low oral doses of ethanol in the presence and absence of ranitidine and to assess the effect of these concentrations on cognitive performance. An active control group (0.45 g per kg alcohol) was included as a validation of the methodology used. A randomized, double-blind, placebo-controlled, four-way crossover study was performed in eight healthy males. Subjects received a 20-min intravenous infusion of 0.10, 0.15, or 0.45 g per kg alcohol or placebo. Blood samples were obtained to measure BAC and psychometric effects were assessed over 8 h. A pharmacokinetic model was used to fit simultaneously the BAC--time profiles of all three doses for each subject. Cognitive improvement was assessed using digit symbol substitution, continuous tracking, and divided attention tests. Analysis of variance was conducted in order to compare peak blood alcohol impairment (E(max)) and area under the alcohol impairment--time curve (AUEC) across treatments. Observed median peak BAC (C(max)) for 0.10- and 0.15-g/kg dose groups (median BACs 15.2 and 27 mg/dl, respectively) were very similar to the target C(max) (13 and 26 mg/dl). Analysis of variance of AUEC and E(max) showed difference in impairment measures after the 0.10- and 0.15-g/kg doses. A significant difference in impairment measures between placebo and the active control, 0.45 g/kg (median BAC of 110 mg/dl) was observed, indicating that the methodology was capable of detecting significant psychomotor effects at the legal limit of BAC. Results indicated that the BAC increments from 15 to 27 mg/dl are not associated with significantly impaired performance and, hence, it is unlikely that increases in BAC of this magnitude, such as those caused by ranitidine therapy, are of any clinical relevance.

Fat absorption and gastroenteric pH profile in postsurgical pancreatic insufficiency: role of the association of H2-receptor antagonists with pancreatic enzymes.

The complete control of steatorrhea in post-surgical exocrine pancreatic insufficiency is difficult. The aim of this study was to evaluate the effect of the association of ranitidine with pancrelipase om fecal fat excretion in patients who had undergone a pancreatoduodenectomy with suppression of the exocrine pancreatic secretion by Neoprene injection. Ten patients were studied 1 year after surgery. Steatorrhea was measured as an integrated test of 3-day stools, while patients were kept on a diet of 100 g lipid/day, with their usual enzyme supplementation therapy (16,050 USP units of lipase/meal). A basal 24-h gastroenteric pH profile was also obtained. In the following month, patients had ranitidine (150 mg twice a day) in addition to pancrelipase. Then steatorrhea and gastroenteric pH were reassessed. Mean fecal fat was 26.9 (SD 13.7) g/day without ranitidine and 30.5 (SD 13.9) g/day during combined treatment. Body weight and nutritional parameters did not show any significant variation after ranitidine administration. Even in the absence of ranitidine, postprandial gastroenteric pH values were always > 4; the H2-receptor antagonist only reduced fasting gastric acidity. In conclusion, the gastroenteric pH and fecal fat determinations showed that ranitidine is not useful in patients with total postsurgical exocrine pancreatic insufficiency.

Influence of hormonal treatment on the response of the rat isolated uterus to histamine and histamine receptor agonists

The response of the isolated uterus to histamine and histamine agonists was investigated in progesterone- and oestrogen-treated rats. The uterine inhibitory responses to histamine and 4-methylhistamine (a histamine H 2 receptor agonists) were similar in KCl-contracted uteri from progesterone- and oestrogen-treated rats. The histamine H 1 receptor agonist, 2-pyridyl-ethylamine, produced a relaxant response only in progesterone dominant uterus. This was inhibited by the histamine H 1 receptor antagonist. In the rat isolated uterus which was not preconstricted by KCl, neither histamine, 4-methylhistamine, nor 2-pyridyl-ethylamine produced any effect in the presence or absence of ranitidine. Ranitidine competitively antagonized the histamine-relaxant uterine response in oestrogen-treated rats (pA 2 = 7.21 (6.83–7.58)), but not in progesterone-treated rats, except in the presence of clemizole (10−7M) when the pA 2 value of ranitidine against histamine was similar to that obtained in oestrogen-treated rats (pA 2 = 6.74 (6.64–6.85)). These results indicate that treatment with ovarian steroids influences responses mediated by the histamine receptors of the isolated rat uterus. Both histamine H 2 and H 1 receptors contribute to the uterine inhibitory effect of histamine in progesterone-treated rats.

A lack of pharmacokinetic interaction between ranitidine and piroxicam

The effects of piroxicam (40 mg) on the pharmacokinetics of ranitidine (150 mg) and of ranitidine (150 mg bid) on the pharmacokinetics of piroxicam (20 mg) were assessed in two 2-way crossover studies in two groups of 18 healthy male subjects. In the first study there were no statistically significant differences between the pharmacokinetic variables for ranitidine in the presence or absence of piroxicam. The mean maximum plasma concentration (Cmax) was 467 ng.ml-1 for ranitidine alone and 466 ng.ml-1 in the presence of piroxicam: mean area under the plasma concentration vs time curve (AUC) was 2460 h.ng ml-1 and 2551 h.ng ml-1 respectively; and the mean terminal half-life (t 1/2) was 3.6 h and 3.8 h respectively. In the second study there were no statistically significant differences between the pharmacokinetic variables for piroxicam in the presence or absence of ranitidine. The mean Cmax was 2.1 micrograms.ml-1 in the presence of placebo and 2.0 micrograms.ml-1 in the presence of ranitidine respectively; mean AUC was 133 h.microgram ml-1 and 137 h.microgram ml-1 respectively, and the mean t 1/2 was 53.6 h and 54.5 h respectively.