Distribution of bismuth in the rat after oral dosing with ranitidine bismuth citrate and bismuth subcitrate. 1998

J Canena, and J Reis, and A S Pinto, and A M Santos, and J Leitão, and T Pinheiro, and M G Quina
Clínica Universitária de Medicina Interna e Gastrenterologia da Universidade, Nova de Lisboa--Hospital de Pulido Valente, Lisbon, Portugal.

Bismuth preparations are used world-wide for the management of peptic ulcer disease, for eradication of Helicobacter pylori, and in the prevention and treatment of diarrhoea. However neurological toxicity of bismuth has always been a major concern and evidence has been found of the absorption of bismuth. Recent studies have suggested that the absorption of bismuth increases when bismuth salts are used with ranitidine hydrochloride. The absorption and deposition of bismuth as a result of the use of the new drug ranitidine bismuth citrate have not been yet clarified. After 15 days of twice daily oral gavage with bismuth subcitrate, 13.7 mg kg(-1) day(-1) to eight rats, deposition of bismuth was found in all the tissues studied, especially the kidney (30.81 +/- 8.59 microg g(-1) dry weight). A similar pattern of distribution and tissue concentrations was found when bismuth subcitrate was given with ranitidine hydrochloride 8.6 mg kg(-1) day(-1) to another eight rats, although this combination resulted in lower brain levels (3.12 + 1.31 microg g(-1) dry weight) than after administration of bismuth subcitrate alone (4.77 +/- 0.97 microg g(-1) dry weight). When six rats were given ranitidine bismuth citrate by gavage at 22.8 mg kg(-1) day(-1) for 15 days, kidney levels were lower (4.24 +/- 1.75 microg g(-1) dry weight) and brain levels were below detection limits; the bismuth concentrations in the faeces from this group were also significantly lower (1603 +/- 104.0 microg g(-1) dry weight) than for the two other groups. After dosing with bismuth alone or in association with ranitidine hydrochloride, bismuth was detected in several organs and deposition was not influenced by gastric pH. Blood levels correlate poorly with organ deposition and brain deposition was not always associated with encephalopathy. After administration of ranitidine bismuth citrate, significantly lower concentrations of bismuth were found in the kidney and bismuth was not detectable in the brain, suggesting lower bismuth absorption. This was confirmed by higher levels in the faeces after dosing with ranitidine bismuth citrate. Thirty days after dosing with ranitidine bismuth citrate or bismuth subcitrate, bismuth could not be detected in any of the organs examined but could be found in the urine. In conclusion, bismuth was deposited in the kidney, brain, lung and liver of rats after oral dosing with bismuth subcitrate. After oral dosing with an equivalent amount of bismuth in the form of ranitidine bismuth citrate, significantly lower concentrations of bismuth were deposited in the kidney; in the brain bismuth was not detectable.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D009942 Organometallic Compounds A class of compounds of the type R-M, where a C atom is joined directly to any other element except H, C, N, O, F, Cl, Br, I, or At. (Grant & Hackh's Chemical Dictionary, 5th ed) Metallo-Organic Compound,Metallo-Organic Compounds,Metalloorganic Compound,Organometallic Compound,Metalloorganic Compounds,Compound, Metallo-Organic,Compound, Metalloorganic,Compound, Organometallic,Compounds, Metallo-Organic,Compounds, Metalloorganic,Compounds, Organometallic,Metallo Organic Compound,Metallo Organic Compounds
D011899 Ranitidine A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. AH-19065,Biotidin,N (2-(((5-((Dimethylamino)methyl)-2-furanyl)methyl)thio)ethyl)-N'-methyl-2-nitro-1,1-ethenediamine,Ranisen,Ranitidin,Ranitidine Hydrochloride,Sostril,Zantac,Zantic,AH 19065,AH19065,Hydrochloride, Ranitidine
D001729 Bismuth A metallic element that has the atomic symbol Bi, and atomic number 83. Its principal isotope is Bismuth 209.
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D006635 Histamine H2 Antagonists Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood. Antihistaminics, H2,H2 Receptor Blockader,Histamine H2 Antagonist,Histamine H2 Blocker,Histamine H2 Receptor Antagonist,Histamine H2 Receptor Antagonists,Histamine H2 Receptor Blockader,Histamine H2 Receptor Blockaders,Antagonists, Histamine H2,Blockaders, Histamine H2 Receptor,H2 Receptor Blockaders,Histamine H2 Blockers,Receptor Antagonists, Histamine H2,Receptor Blockaders, H2,Antagonist, Histamine H2,Blockader, H2 Receptor,Blockaders, H2 Receptor,Blocker, Histamine H2,Blockers, Histamine H2,H2 Antagonist, Histamine,H2 Antagonists, Histamine,H2 Antihistaminics,H2 Blocker, Histamine,H2 Blockers, Histamine,Receptor Blockader, H2
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations

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