Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D01467 (Roxatidine acetate hydrochloride)
 4 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effects of a new compound, N-[3-[3-(piperidinomethyl)phenoxy]-propyl]-2-(2-hydroxyethyl-1- thio)acetamido.2-(4-hydroxy benzoyl)benzoate (Z-300), on the histamine H2-receptor, gastric secretion in rats and dogs, and acute gastro-duodenal lesions or chronic gastric ulcers in rats. Roxatidine acetate hydrochloride (roxatidine), a known histamine H2-receptor antagonist, was used as a reference compound. The pA2 values for Z-300 and roxatidine for the isolated guinea pig atrium were 6.8 and 7.0, respectively. These agents at less than 10(-5) M did not affect the contraction of guinea pig ileum in response to carbachol. Z-300, administered either orally or parenterally, significantly inhibited the basal and histamine-stimulated gastric acid secretion in rats. Gastric acid secretion stimulated by histamine, pentagastrin or carbachol in Heidenhain pouch dogs was also significantly inhibited by the compound. The effect persisted for greater than 7 hr in the case of histamine-stimulation. Oral Z-300 significantly protected the gastric mucosa from water-immersion stress-, indomethacin-, aspirin- and HCl.ethanol-induced lesions and protected the duodenal mucosa against mepirizole- and cysteamine-induced ulcers. These effects on gastric secretion and lesion formation were, as a whole, stronger than those observed with roxatidine. Z-300, but not roxatidine, significantly accelerated the spontaneous healing of acetic acid ulcers induced in rats and prevented the delay in ulcer healing caused by indomethacin. The mechanism of action of Z-300 on acute lesions and chronic ulcers appears to be mostly related to its potent antisecretory and mucosal-protective activities.
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PMID:Effects of a new histamine H2-receptor antagonist, Z-300, on gastric secretion and gastro-duodenal lesions in rats: comparison with roxatidine. 135 78

The effects of roxatidine acetate hydrochloride and cimetidine during multiple dosing on the pharmacokinetics of theophylline was studied in nine healthy volunteers, five smokers and four non-smokers, in comparison with placebo treatment. Cimetidine reduced the terminal elimination rate constant and the total body clearance of theophylline from 0.119 to 0.101 h-1 (p less than 0.05) and from 31.2 to 26.5 ml/min (p less than 0.05), respectively, in comparison with those of placebo. There was no significant change in the volume of distribution (16.3 l for placebo and 15.5 l for cimetidine) and the renal clearance (4.5 ml/min for placebo and 3.9 ml/min for cimetidine). Roxatidine acetate hydrochloride did not significantly influence theophylline disposition in comparison with placebo treatment. The interaction of cimetidine on theophylline disposition was observed in both smokers and non-smokers, but the degree was greater in smokers.
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PMID:Effects of roxatidine acetate hydrochloride and cimetidine on the pharmacokinetics of theophylline in healthy subjects. 273 1

Roxatidine acetate hydrochloride capsule is slowly absorbed from the gastrointestinal tract, and its acid suppressive effect on the stomach is long-lasting compared with other H2-blockers. The reduction of gastric juice in perioperative period is considered advantageous for patients not only because it decreases the risk for aspiration pneumonia but also because it reduces the risk of bronchial spasm induced by gastroesophageal reflux of acidic gastric content. The effects of single oral administration of roxatidine acetate hydrochloride 150 mg at night before the operation on the volume and pH of gastric juice were investigated during anesthesia using two types of anesthetic agents (isoflurane and propofol) in 93 patients of three age groups (group Y: age 20-40, group M: age 41-64, group O: age 65 <). The effect of roxatidine on reduction of gastric juice was found at the time of anesthetic induction and 2 hours after the induction in any age group with either anesthetic agent. The serum concentration of roxatidine at the time of induction was much higher in group O. The value of residual concentration of roxatidine 20 hours after oral intake was estimated from the intraoperative measurements of serum concentration. The results suggest that single administration at night before the operation is sufficient for the oldest group, but an additive dose is recommended for the younger groups.
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PMID:[Clinical evaluation of roxatidine acetate hydrochlorides as a preanesthetic medication]. 1124 65

Roxatidine acetate hydrochloride (ROX, 2-acetoxy-N-[3-[m-(1-piperidinylmethyl)phenoxy]propyl]acetamide hydrochloride, CAS 78273-80-0), a histamine 2 (H2)-receptor antagonist, has been clinically applied for the treatment of gastritis, gastric and duodenal ulcers. There is no report on the identification of the metabolic enzyme of M-1 (2-hydroxy-N-[3-[m-(1-piperidinylmethyl)phenoxy]propyl]acetamide), the pharmacologically active metabolite, in humans. In this study, the Cytochrome P450 (CYP or P450) enzymes which participate in the metabolism of ROX were identified using human liver microsomes and S9 fractions. M-1 was converted to M-4 (3-[m-(1-piperidinyl-methyl)phenoxy]propylamine) by the enzyme reaction with the S9 but not with microsomes. M-4 was further metabolized to M-5 (3-[m-(1-piperidinylmethyl)phenoxy]propanol) by microsomes. The metabolism was inhibited by coumarin and anti-CYP2A1 serum. (3-[m-(1-piperidinylmethyl)-phenoxy]propionic acid) and M-3 (m-(1-piperidinylmethyl) phenol) formation from M-5 were inhibited by quinidine and anti-CYP2D6 serum. Moreover, M-5 was converted to M-2 and M-3 by cDNA-expressed CYP2D6. In conclusion, this study shows that microsomal enzymes do not participate in the clearance of the active metabolite M-1, CYP2A6 primarily catalyzes M-5 formation from M-4, and CYP2D6 primarily catalyzes M-2 and M-3 formation from M-5 in humans.
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PMID:Cytochrome P450 enzymes involved in the metabolic pathway of the histamine 2 (H2)-receptor antagonist roxatidine acetate by human liver microsomes. 1155 26