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PubMed2005

[Effect of acid suppression therapy for eradicating Helicobacter pylori infection on bismuth absorption from colloidal bismuth pectin].

OBJECTIVE: To investigate whether acid suppression therapy influences the absorption of bismuth from colloidal bismuth pectin (CBP). METHODS: 48 male SD rats were randomly divided into five groups to be administer with different medicines once a day for 14 days: group A1 (administered with CBP only and killed on the cessation day of administration), group B1 (administered with CBP only and killed 8 weeks after the cessation of administration), group A2 [administered with CBP + amoxicillin (AMO) + metronidazole (MTR) + losec and killed on the cessation day of administration], group B2 (administered with CBP + AMO + MTR + losec and killed 8 weeks after the cessation of administration), and control group (administered with distilled water). The kidney issue sections were counterstained after AMG development. The bismuth deposited in tissues was observed by microscopy. The gray level of kidney tissue sections were measured and compared through image processing program. The deposition of bismuth and the degrees of cell organ's impairment were observed by electron microscopy. By using electron probe microanalysis bismuth was identified from the chemical elements in the specimens. RESULTS: Under the light microscopy, black-brown granules were discovered in the cell bodies of the proximal convoluted renal tubule. The amounts of bismuth accumulated in kidney of the 2 quadruple therapy groups were much more than those of the 2 single compound therapy groups (all P < 0.05). The amount of bismuth accumulated in kidney on the cessation day of administration was more than that eight weeks later (both P < 0.01). Under electron microscopy, black-brown granules were observed exclusively in the lysosomes of the proximal convoluted renal tubule cell. Electron microscopy found cell impairment in the quadruple therapy groups. Impairment of these cells could be recovered 8 weeks after the cessation of administration. CONCLUSION: Acid suppression therapy causes an increase of absorption and accumulation of bismuth from CBP in the kidney. Bismuth can be accumulated in the cell bodies of proximal convoluted renal tubule after its absorption. The absorbed bismuth can be discharged out of the body via kidney. Large amounts of bismuth accumulation in kidney can impair the functions of proximal convoluted renal tubule cells.

Amoxicillin↗
PubMedDate not supplied

[The relationship between the course of bismuth encephalopathy and the amount of bismuth in blood and urine].

Study of the course of bismuth encephalopathy following the ingestion of a bismuth salt in relation to blood and urinary bismuth levels indicates a close parallel between the improvement in the clinical picture and the decrease in the degree of toxic impregnation of the body. This confirms the direct responsibility of bismuth for the disorder. Regression of myocolonic movements goes with the fall in blood bismuth levels, whilst improvement in the confusional syndrome is aomewhat delayed. There is a significant correlation between bismuth levels in the blood and urine. The excretion of bismuth is slow, and the persistence of blood and urinary bismuth levels higher than normal for several weeks after the acute phases and the interruption of the ingestion of bismuth salts reflects the existence of stable bonds between the metal and cellular constituents. The authors have observed a non-negligeable solubility of bismuth sub-nitrate in certain drinking waters, which brings up the hypothesis of a possible role of the hydrosobulity of bismuth in the pathogenesis of the intoxication.

Adult↗
PubMed2000

Site of bismuth absorption from bismuth subsalicylate: implications for treatment of colonic conditions.

Poorly absorbed bismuth preparations may benefit a variety of chronic colonic conditions including ulcerative colitis. Bismuth-induced neurotoxicity is a potential complication of the chronic use of these preparations, and a less-absorbable form of bismuth is needed. If bismuth absorption occurs primarily in the upper gut, a delayed-release bismuth preparation could reduce absorption. We studied the site of bismuth absorption from bismuth subsalicylate (BSS) in rats. For 15 days, BSS (50 mg/day) was ingested or infused directly into the cecum via a chronically implanted cannula. Oral BSS resulted in serum and urine bismuth levels many times higher (3.5 +/- 0.3 microg/liter and 1,570 +/- 286 microg/g creatinine, respectively) than with cecal administration (undetectable (<1.5 microg/liter) and 75 +/- 25 microg/g creatinine). Thus, bismuth absorption from BSS occurred almost entirely in the upper gut. These findings provide a rationale for a similar study of delayed-release bismuth preparations in humans.

Absorption↗
PubMed1985

Uptake and subcellular localisation of bismuth in the gastrointestinal mucosa of rats after short term administration of colloidal bismuth subcitrate.

Despite the topical action of colloidal bismuth subcitrate in promoting the healing of peptic ulcers, slight absorption of bismuth from the gastrointestinal tract has been reported in colloidal bismuth subcitrate-treated animals and man. The uptake and subcellular distribution of bismuth by the gastrointestinal tract of rats after 24 hours of colloidal bismuth subcitrate administration was studied. Mucosal uptake of bismuth (mean +/- SEM nmol/g protein) by gastric fundus (8.85 +/- 1.0) and antrum (7.23 +/- 1.50) was similar, but was significantly less than duodenum (19.2 +/- 3.7, p less than 0.05), jejunum (26.9 +/- 2.4, p less than 0.001) or ileum (22.4 +/- 2.2, p less than 0.001). Bismuth concentrations in antral and duodenal mucosae fell progressively over 72 hours to approximately 10% of initial concentrations (p less than 0.02). Subcellular fractionation studies of colloidal bismuth subcitrate treated duodenal enterocytes showed a brush border membrane and cytosolic localisation. These data suggest that some gastrointestinal mucosal uptake of bismuth occurs in colloidal bismuth subcitrate treated rats.

Animals↗
PubMed1990

[Alleviation of cisplatin toxicity by high-dose bismuth subnitrate and pharmacokinetics of bismuth subnitrate and cisplatin].

Twelve patients with several malignant neoplasms, including lung and gastrointestinal carcinoma were treated with high-dose Cisplatin and high-dose Bismuth Subnitrate. Therapeutic efficacy and protective effect of high-dose Bismuth Subnitrate on toxicity of Cisplatin were evaluated in twenty-five courses of treatment. The Pharmacokinetics of Bismuth Subnitrate and Cisplatin were also studied in several courses. Bismuth Subnitrate was administered orally at a dose of 150 mg/kg/day for 10 days and a dose of 80-150 (Mean 108) mg/m2 of Cisplatin was administered intravenously on the day six of Bismuth Subnitrate administration. Toxicities of high-dose Cisplatin were minimal under administration of high-dose Bismuth Subnitrate and therapeutic efficacy was observed in several patients. The pharmacokinetics of Bismuth Subnitrate in plasma and urine demonstrated that 10 days administration of high-dose Bismuth Subnitrate was appropriate to maintain adequate concentration of Bismuth for preinduction of Metallothionein in organs. The pharmacokinetics of Cisplatin in plasma and urine demonstrated that deposition of total and ultrafilterable (free) platinum in blood were well described by a biphasic manner with a very rapid first phase and a very prolonged second phase, and that urine excretion of platinum was similar to the conventional manner. This study demonstrated that concurrent administration of high-dose Bismuth Subnitrate can permit the administration of high-dose Cisplatin with minimal toxicity and appropriate antitumor effect.

Adult↗
PubMed1979

Bismuth intoxication: bismuth level in pig brain lipids and in subcellular fractions.

Experimental intoxications of pigs were performed. It seems to be confirmed that bismuth crosses the blood-brain barrier. An organic derivative, trivinyl-bismuth, is more active than the inorganic salt of bismuth. In the brain, bismuth is preferentially found in synaptosomes. Bismuth is found in brain lipids of control pigs at very low levels. In intoxicated pigs, the level of bismuth is increased mainly in cerebellum and then in thalamus. Bismuth is partly associated to lipids. There is not a correlation between the level of bismuth in blood and in brain lipids. However, in the trivinyl intoxicated pig, a high level of blood bismuth is concomittant to a high level of brain lipid bismuth. The high content of this metal in cerebellum lipid extract may be of functional significance.

Animals↗
PubMed1997

Cytoprotective effect of bismuth subsalicylate in indomethacin-treated rats is associated with enhanced mucus bismuth concentration.

BACKGROUND: Bismuth compounds prevent gastric injury from the short-term administration of nonsteroidal anti-inflammatory drugs. We studied the mechanisms underlying the gastroprotective actions of bismuth subsalicylate against indomethacin-induced injury in rats. METHODS: An in vivo microscopic technique was used in which acid output, surface cell intracellular pH (pHi), gastric mucus gell thickness and mucosal blood flow were measured simultaneously. Concentrations of bismuth in mucus were measured by atomic absorption. RESULTS: Indomethacin (60 mg/kg) significantly thinned the mucus gel layer and augmented the decrease of pHi during luminal acid superfusion, consistent with a weakened gastric mucosal barrier to acid. Bismuth subsalicylate partially reversed this effect of indomethacin on pHi, consistent with gastroprotection. Neither a prostaglandin-inhibiting but non-injurious dose of indomethacin (5 mg/kg), bismuth subsalicylate, or their combination affected mucus gel thickness or pHi homeostasis. In separate experiments, indomethacin (60 mg/kg) significantly increased gastric mucus bismuth concentration in rats given bismuth subsalicylate. CONCLUSION: Bismuth accumulation in the gastric mucus during the evolution of mucosal injury may play an important role in the gastroprotective effect of bismuth subsalicylate against indomethacin injury.

Animals↗
PubMedDate not supplied

Bismuth-based triple therapy with bismuth subcitrate, metronidazole and tetracycline in the eradication of Helicobacter pylori: a randomized, placebo controlled, double-blind study.

OBJECTIVE: To determine the rate of Helicobacter pylori eradication following bismuth-based triple therapy with colloidal bismuth subcitrate, tetracycline hydrochloride and metronidazole. PATIENTS AND METHODS: One hundred and eleven patients were randomly assigned, in a two to one ratio, to colloidal bismuth subcitrate 120 mg qid plus metronidazole 250 mg qid plus tetracycline 500 mg qid (Gastrostat), or matching placebo tablets and capsules for 14 days. Presence or absence of H pylori was documented by histology at entry and at least 28 days after treatment. Patients had dyspeptic symptoms with or without a history of peptic ulcer. Patients with any previous attempt(s) at eradication of H pylori, who used bismuth, antibiotics, H2 receptor antagonists or proton pump inhibitors in the previous four weeks were excluded. RESULTS: Fifty-three of 59 (90%) patients on bismuth-based treatment and only one of 35 (3%) on placebo achieved eradication by per protocol analysis. Fifty-three of 65 (82%) patients on bismuth-based treatment achieved eradication, while only two of 34 (5%) achieved eradication on placebo by intention to treat analysis. Eradication rates for bismuth-based treatment across sites ranged from 83% to 100%. Only two patients in the bismuth-based treatment group (4%) and one in the placebo group (3%) discontinued treatment because of adverse events. CONCLUSIONS: Colloidal bismuth subcitrate plus metronidazole plus tetracycline, given in the doses studied for 14 days, is safe and highly effective against H pylori infection and would be appropriate as a first-line therapy for eradication.

Adolescent↗
PubMed2004

Determining the background levels of bismuth in tissues of wild game birds: a first step in addressing the environmental consequences of using bismuth shotshells.

Bismuth shotshells have been approved as a "nontoxic" alternative to lead in North America. Approval was based on a limited number of studies; even background levels of bismuth in wildfowl were unknown. We report on the concentration of bismuth (and lead) in muscle and liver tissues of wildfowl (Anas platyrhynchos, Anas acuta, Anas crecca, Branta canadensis, Chen caerulescens) harvested with lead shotshell. Average liver-bismuth levels detected in the present study (e.g., teal, 0.05 microg/g dw; mallard, 0.09 microg/g dw) suggest analytical error in other studies examining the effects of bismuth in birds. Significant positive relationships between bismuth- and lead-tissue levels for muscle when all species were combined (and for B. canadensis and C. caerulescens separately) can be explained by noting that bismuth is a contaminant of lead. Thus, more research is recommended to confirm the appropriateness of bismuth as a "nontoxic" shot alternative.

Animals↗
PubMed1994

Omeprazole-induced increase in the absorption of bismuth from tripotassium dicitrato bismuthate.

OBJECTIVE: Omeprazole is an effective drug for treating active peptic ulcer, whereas tripotassium dicitrato bismuthate can prevent ulcer relapse if Helicobacter pylori is eradicated. Because both drugs will be given concomitantly, drug interactions have to be considered, especially since absorption of bismuth may be dependent on intragastric pH, which will be elevated by omeprazole. METHODS: In a placebo-controlled crossover study, six healthy volunteers received daily oral doses of 40 mg omeprazole for 1 week and a single oral dose of 240 mg tripotassium dicitrato bismuthate. Plasma concentration-time profiles (AUC) and urinary excretion (Ae) of bismuth were measured by atomic absorption spectrophotometry and plasma levels of omeprazole by HPLC. In addition, intragastric pH values were monitored for 8 hours. RESULTS: As expected, control mean pH values (2.1) were evaluated to 4.7 by omeprazole (p = 0.001), which was eliminated with a half-life of 1.3 +/- 0.7 hours (mean +/- SD) and an oral clearance of 387 +/- 221 ml/min. The increase of intragastric pH was related to the AUC of omeprazole (r = 0.89; p = 0.017). Omeprazole increased absorption of bismuth because AUC and Ae were higher (p < or = 0.05) during omeprazole treatment (172 +/- 158 micrograms/L.hr and 1.9 +/- 2.0 mg/8 hr, respectively) compared with placebo (46 +/- 33 micrograms/L.hr and 0.27 +/- 0.28 mg/8 hr, respectively). A significant correlation (r = 0.85; p = 0.038) could be observed between intragastric pH differences and Ae values. CONCLUSIONS: Omeprazole caused an increase of the systemic availability of bismuth from tripotassium dicitrato bismuthate. Whether this pharmacokinetic interaction between both drugs results in alterations of H. pylori eradication or the toxic potential of bismuth remains to be elucidated by further clinical studies.

Administration, Oral↗
PubMed1996

Pharmacokinetics of bismuth and ranitidine following single doses of ranitidine bismuth citrate.

1. The pharmacokinetics of bismuth and ranitidine derived from ranitidine bismuth citrate given in single oral doses ranging from 200 mg to 1600 mg were evaluated in healthy subjects. 2. Bismuth was only minimally absorbed (< 0.5% of the amount dosed) after administration of ranitidine bismuth citrate, and peak plasma concentrations never exceeded 33 ng ml-1 in any subject. Plasma concentrations and urinary recoveries of bismuth at doses up to and including 800 mg were relatively constant and not proportional to dose. Bismuth absorption was increased more than proportionally with the dose at 1600 mg. 3. The pharmacokinetics of ranitidine after administration of ranitidine bismuth citrate were dose-proportional and consistent with previous observations for ranitidine administered alone. 4. Ranitidine bismuth citrate was well-tolerated in single oral doses of up to 1600 mg.

Adult↗
PubMed1996

Ranitidine bismuth citrate: a novel anti-ulcer agent with different physico-chemical characteristics and improved biological activity to a bismuth citrate-ranitidine admixture.

BACKGROUND: Ranitidine bismuth citrate (RBC) is a new chemical entity for the treatment of peptic ulcer disease. RESULTS: RBC is freely soluble in water (more than 600 mg/mL at pH 4.6), whereas an equimolar admixture of its component molecules, bismuth citrate and ranitidine, formed an almost totally insoluble suspension. Even at very low pH values (around 2.0), the solubility of bismuth in ranitidine bismuth citrate was at least two-fold better than in the admixture. Comparison of several physico-chemical characteristics indicated that RBC possessed significantly different melting point properties, X-ray powder diffraction patterns, infra-red spectra and 13C-NMR solid-state spectra to the admixture. Ranitidine bismuth citrate inhibited human pepsin isoenzymes 1, 2, 3 and 5 but the admixture was inactive. RBC showed approximately two-fold greater anti-Helicobacter pylori activity in vitro than the admixture (geometric mean minimum inhibitory concentrations of 12.5 and 25.7 mg/L, respectively) and was more rapidly bactericidal. In a mouse model of gastric H. pylori colonization, 200 mg/kg of bismuth, given as RBC, eradicated the organism from all mice while only 10% of infections were eradicated by equivalent levels of bismuth in admixture form. CONCLUSION: It is believed that the significantly greater solubility of RBC, especially at lower pH values, is highly relevant to its better antipepsin and anti-H. pylori action compared to the insoluble admixture of bismuth citrate and ranitidine.

Animals↗
PubMed1989

Bismuth accumulates in the body during treatment with tripotassium dicitrato bismuthate.

Bismuth concentration was measured in plasma, dried leucocytes and urine in nine patients before, during and after treatment with tripotassium dicitrato bismuthate (De-Noltab 2 b.d.) for 6 weeks. During treatment there was an 8.5-fold rise in median plasma bismuth concentration (P less than 0.01), a non-significant doubling of leucocyte bismuth content, and a 349-fold rise in 24-h urinary bismuth excretion (P less than 0.01). The significantly increased urinary bismuth excretion continued for at least 3 months after cessation of treatment with tripotassium dicitrato bismuthate, indicating accumulation of bismuth during treatment with this drug.

Adult↗
PubMed2005

Metabolism of bismuth subsalicylate and intracellular accumulation of bismuth by Fusarium sp. strain BI.

Enrichment cultures were conducted using bismuth subsalicylate as the sole source of carbon and activated sludge as the inoculum. A pure culture was obtained and identified as a Fusarium sp. based on spore morphology and partial sequences of 18S rRNA, translation elongation factor 1-alpha, and beta-tubulin genes. The isolate, named Fusarium sp. strain BI, grew to equivalent densities when using salicylate or bismuth subsalicylate as carbon sources. Bismuth nitrate at concentrations of up to 200 muM did not limit growth of this organism on glucose. The concentration of soluble bismuth in suspensions of bismuth subsalicylate decreased during growth of Fusarium sp. strain BI. Transmission electron microscopy and energy-dispersive spectroscopy revealed that the accumulated bismuth was localized in phosphorus-rich granules distributed in the cytoplasm and vacuoles. Long-chain polyphosphates were extracted from fresh biomass grown on bismuth subsalicylate, and inductively coupled plasma optical emission spectrometry showed that these fractions also contained high concentrations of bismuth. Enzyme activity assays of crude extracts of Fusarium sp. strain BI showed that salicylate hydroxylase and catechol 1,2-dioxygenase were induced during growth on salicylate, indicating that this organism degrades salicylate by conversion of salicylate to catechol, followed by ortho cleavage of the aromatic ring. Catechol 2,3-dioxygenase activity was not detected. Fusarium sp. strain BI grew with several other aromatic acids as carbon sources: benzoate, 3-hydroxybenzoate, 4-hydroxybenzoate, gentisate, d-mandelate, l-phenylalanine, l-tyrosine, phenylacetate, 3-hydroxyphenylacetate, 4-hydroxyphenylacetate, and phenylpropionate.

Biomass↗
PubMed1992

Bismuth absorption from 205Bi-labelled pharmaceutical bismuth compounds used in the treatment of peptic ulcer disease.

The absorption of bismuth from five 205Bi-labelled pharmaceutically used bismuth compounds was studied in man. From single oral doses of all compounds under investigation only less than 0.1% bismuth was absorbed and excreted with the urine. A significantly higher absorption was observed from the colloidal bismuth subcitrate (0.042% of the dose) and the basic bismuth gallate (0.038%) than from the basic bismuth salicylate, nitrate, and aluminate (0.005-0.002%). No retention of bismuth in the whole body was found from the single dose experiment. The biologic fast-term half-lives of absorbed bismuth were calculated to be 0.12 and 1.5 days.

Adult↗
PubMed2002

[The difference of the bismuth absorption from a single colloidal bismuth pectin therapy and quadruple therapy for eradicating Helicobacter pylori infection].

OBJECTIVE: To investigate whether the quadruple therapy influences the absorption of bismuth from Colloidal Bismuth Pectin (CBP). METHODS: 24 male Wistar rats weighing from 400 g to 500 g were randomly divided into two groups: CBP group (group A(1)) and CBP+AMO+MTR+ LAN group (group A(2)). The serum bismuth concentration was observed at 0,1,2,3,4,5,6 hour after these medicines were fed. Other 24 male Wistar rats weighing from 200 g to 250 g were randomly divided into two groups: CBP group (group B( 1)), CBP+AMO+MTR+LAN group (group B(2)). These medicines had been taken every day for 14 days. The accumulation of bismuth in the heart, brain, kidney and liver of rats were detected eight weeks later. RESULTS: The serum peak value of bismuth is not significantly different between group A(1) and group A(2) (P > 0.05), but the peak time of bismuth of the group A(2) is one hour earlier than that of group A(1). The amounts of the accumulation of bismuth in the kidney are 154 +/- 15 ng/g and 212 +/- 20 ng/g in the group B(1) and B(2) respectively at the eighth week after the medicines were fed in rats with a significant difference (P < 0.05). CONCLUSION: The quadruple therapy causes an increase of the absorption and the accumulation of bismuth from CBP in the kidney in rats.

Absorption↗
PubMed1994

Pharmacological effects of metronidazole+tetracycline+bismuth subcitrate versus omeprazole+amoxycillin+bismuth subcitrate in Helicobacter pylori-related gastritis and peptic ulcer disease.

PURPOSE: Two 4-week triple-therapy treatment regimens, metronidazole+tetracycline+bismuth subcitrate and omeprazole+amoxycillin+bismuth subcitrate, were compared in a randomly allocated double-blind trial for their efficacy in eradicating Helicobacter pylori from the gastric mucosa of patients with gastritis and/or peptic ulcer disease. PATIENTS AND METHODS: The presence of gastritis and/or peptic ulcers was confirmed by endoscopy in all patients included in the study. To evaluate drug effects, we used the urease test on gastric mucosa, and haematoxylin-eosin and specific Giemsa stains on biopsy tissues obtained by endoscopic procedures; we also evaluated the improvement in clinical symptoms before and after the 4-week treatments. RESULTS: Among 164 patients with gastritis and/or peptic ulcers, H. pylori infection was confirmed in 93.9% (154 patients) by the urease test and in 87.8% (144 patients) by haematoxylin-eosin stain. Following 4 weeks of treatment with both combination regimens, negative conversion rates by the urease test and haematoxylin-eosin staining and rates of recovery from clinical symptoms were similar in both regimens (metronidazole+tetracycline+bismuth subcitrate: 82.3, 72.9 and 73.9%; omeprazole+amoxycillin+bismuth subcitrate: 89.6, 83.4 and 76.1%, respectively). Also, the extent of inflammatory activity and the H. pylori score by the Giemsa method indicated high rates of recovery, with improvements to grade 0 (lowest grade) from higher grades with both combination regimens (60.4 and 66.7% of patients taking metronidazole+tetracycline+bismuth subcitrate and 64.6 and 83.3 of those taking omeprazole+amoxycillin+bismuth subcitrate). However, the prevalence of side effects during the 4 weeks of treatment was doubled in the former group compared to the latter (25.5 versus 12.5% of patients). CONCLUSIONS: Significant improvements in biochemical and histopathological findings and in the clinical symptoms of gastritis and/or peptic ulcer disease in patients with a high rate of H. pylori infection were observed equally with both regimens. However, there were notably fewer side effects in patients treated with omeprazole+amoxycillin+bismuth subcitrate. We therefore recommended this regimen in preference to metronidazole+tetracycline+bismuth subcitrate for the treatment of H. pylori-related gastritis and peptic ulcer disease.

Adult↗
PubMed2000

Bismuth biokinetics and kidney histopathology after bismuth overdose in rats.

Bismuth induced nephrotoxicity has been reported to occur after acute overdoses of Bi-containing therapeutic drugs. We studied the development of bismuth induced nephropathy and bismuth biokinetics in rats. Bismuth nephropathy was induced in 33 young adult female Wistar rats weighing ca. 175 g by feeding them a single overdose of colloidal bismuth subcitrate containing 3.0 mmol Bi/kg at (t = 0). Control animals (n = 7) were fed the vehicle only. The animals were sacrificed after 1-48 h. Plasma creatinine increased from 51 +/- 6 micromol/l at t = 0 to 550 +/- 250 micromol/l after 48 h in the experimental group. The S3 segment of the proximal tubule showed epithelial cell vacuolation after 1 h and necrosis after 3 h. Cells of the S1/S2 segment demonstrated vacuolation after 6 h and necrosis after 12 h. Biokinetics of bismuth in blood could best be described with a one-compartment model characterized by an absorption half-life of 0.32 h and an elimination halflife of 16 h. The peak concentration of about 7.0 mg Bi/l was reached after 2 h. In conclusion, cells of the S3 segment of the proximal tubule necrotized first after an oral colloidal bismuth subcitrate overdose and biokinetics of Bi in blood was best described by a one-compartment model.

Absorption↗