Ranitidine, oxidation

Therapeutics. Compounds containing the furan or tetrahydrofuran ring are biologically active and are present in a number of pharmaceutical products. Eurfurjdamine [617-89-0] is an intermediate in the diuretic, furosemide. Tetrahydrofurfurylamine [4795-29-3] may also have pharmaceutical applications. 5-(E)imethyiaininomethyi)furfuryi alcohol [15433-79-17 is an intermediate in the preparation of ranitidine, which is used for treating ulcers. 2-Acet5dfuran [1192-62-7] prepared from acetic anhydride and furan is an intermediate in the synthesis of cefuroxime, a penicillin derivative. 2-Euroic acid is prepared by the oxidation of furfural. Both furoic acid [88-14-2] and furoyl chloride [527-69-5] are used as pharmaceutical intermediates. 

Bismuth salts are still in use. Tripotassium dicitrato-bismuthate and bicitropeptide (a bismuth-peptide complex) are used in the eradication of Helicobacter pylori in combination with antibiotics (SEDA-21,233) (1 ), and ranitidine bismuth citrate is used to treat peptic ulcer (5). Bismuth salicylates are used in other intestinal diseases, such as microscopic colitis (6,7) and collagenous colitis (8). Bismuth subnitrate plus iodoform is used to pack surgical cavities. Bismuth oxide and bismuth subgallate are found in some topical formulations that are used for treating hemorrhoids. Bismuth is also used topically as a bacteriostatic. 

Cimetidine inhibits the liver enzymes associated with oxidative metabolism. Hence, the serum levels of most benzodiazepines affected by this metabolic pathway (aiprazoiam, diazepam, cbiordiazepoxide, fiurazepam, nitrazepam, and triazoiam) were found to be increased when cimetidine was co-administered. Benzodiazepines metabolized by glucuronide conjugation (iorazepam, oxazepam, and temazepam) are not affected by cimetidine. Ranitidine probably has no significant interaction with most benzodiazepines. 

Zantac gives rise to three known metabolites, namely (a) ranitidine N-oxide (Z ) ranitidine S-oxide and (c) desmethyl ranitidine. It is observed to be only a weak inhibitor of the hepatic cytochrome P-450 mixed function oxidation system. The plasma half-life ranges between 2 to 3 hours and it usually gets excreted together with its metabolites in the urine. 

The aromatic furan ring system, though not found in animal metabolism, occurs widely in secondary plant metabolites, especially in terpenoids perillene is a simple example. Vitamin C, ascorbic acid, is at the oxidation level of a trihydroxyfuran, though it assumes an unsaturated lactone tautomeric form. Though one normally associates thiols with unpleasant odours, furfuryl thiol is present in the aroma of roasted coffee. Some 5-nitrofurfural derivatives are important in medicine, Nitrofurazone, a bactericide, is a simple example. Ranitidine is one of the most commercially successful medicines ever developed it is used for the treatment of stomach ulcers. 

Any changes in the pharmacokinetics of paracetamol with these H2-recep-tor antagonists appear to be clinically unimportant. Thus, no special precaution would seem to be necessary when paracetamol is used with cimetidine, nizatidine or ranitidine. The effect of cimetidine on the oxidative metabolism of paracetamol has been investigated as a means of reducing paracetamol hepatotoxicity. However, it appears that cimetidine is not effective for this purpose. ... 

Abernethy DR, GreenblattDJ, E elmanFJSl, Shader RI. Ranitidine does not impair oxidative or conju tive metabolism noninteraction with antipyiine, diazepam, and Icrazepam. Clin Pharmacol Ther (1984) 35,188-92... 

It is believed that cimetidine increases nifedipine levels by inhibiting its oxidative metabolism by the liver. Like ranitidine, it may also increase the bioavailability of nifedipine by lowering gastric acidity. " The mechanisms of the other interactions are probably similar. 

Ranitidine, ranitidine iV-oxide, ranitidine 5-oxide, and desmethylranitidine were baseline resolved in 8 min on a 40°C Cjg column using a 46/5/49 metha-nol/acetonitrile/water (35 mM phosphate buffer at pH 7.0) mobile phase [546]. Often, as in this case, small amounts of acetonitrile added to the mobile phase will yield sharper peaks and, therefore, overall better efficiency. Here, excellent peak shapes were obtained and responses were linear between 10 and lOOOng. 

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