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PubMed1979

Bismuth toxicity in man II. Review of bismuth blood and urine levels in patients after administration of therapeutic bismuth formulations in relation to the problem of bismuth toxicity in man.

A survey of the leterature on bismuth toxicity in man in relation to blood level data, has revealed the necessity of distinguishing between lipid soluble and water soluble organic complexes of bismuth on the one hand and the simple inorganic salts of bismuth on the other hand. A characteristic feature of the former, illustrated by the water soluble bismuth complex triglycollamate, is the high bismuth levels (due to absorption of the complex as such) and the nephrotoxic properties of the compound in man. Bismuth absorption after administration of the simple inorganic salts of bismuth is postulated to occur in the form of ionic bismuth as such, low bismuth levels being characteristic features of such compounds. Bismuth blood and urine levels obtained from patients after administration of a new anti-ulcer drug (Bicitropeptide) in a well controlled clinical trial are discussed and suggest that that this bismuth containing drug behaves pharmacologically in a manner similar to the inorganic bismuth salts in man, low bismuth blood levels and the absence of toxic side effects being conspicuous features of the drug. Based on these considerations, it is proposed that the pharmacologically active bismuth compounds be divided into four different groups depending on structure, stability and solubility. The question as to what constitutes a "toxic bismuth blood level" can only be discussed in relation to the new proposed sub-division of bismuth compounds and is only meaningful if the term is defined to relate only to ionic bismuth (presumably bound to a large extent to blood proteins). Based on information gleaned from the literature and blood level values reported in the clinical trial referred to, it is suggested that bismuth blood level values below 50 micrograms/ml are highly unlikely to be associated with meaningful toxicity in man. Finally, attention is drawn to the reversibility of bismuth toxicity in man as reported by many authors irrespective of the type of bismuth compound concerned.

Animals↗
PubMed1997

Comparative absorption of bismuth in Sprague-Dawley rats following oral administration of preparations containing bismuth sucrose octasulfate, bismuth subsalicylate, and bismuth subcitrate.

The absorption of bismuth from De-Nol (bismuth subcitrate, DN), Pepto-Bismol (bismuth subsalicylate, PB) and bismuth sucrose octasulfate (BISOS) was examined in male Sprague-Dawley rats after a single oral dose of each compound (60mg bismuth). Bismuth was analysed in blood, urine, kidney, brain, liver, and lung using graphite furnace atomic absorption spectrophotometry. Bismuth Cmax averaged 18.4 +/- 11.6 ng mL(-1) for BISOS, 292 +/- 130 ng mL(-1) for DN, and 21.5 +/- 9.63 ng mL(-1 ) for PB. Cmax was significantly lower for BISOS compared to DN (p<0.05) but not significantly different for BISOS compared to PB (p > 0.05). Bismuth AUC was 1356 +/- 474 ng h(-1) mL (-1) for BISOS, 2129 +/- 452 ng h(-l) mL(-1) for DN, and 1824 +/- 919 ng h(-1) for PB, which indicated a lower extent of absorption from BISOS compared to DN. Kidney, liver, and lung levels of bismuth were also significantly lower for BISOS compared to DN (p < 0.05). Bismuth urinary excretion was significantly lower for BISOS (0.04 +/- 0.02%) compared to DN (0.27 +/- 0.15%) but not significantly different compared to PB (0.07 +/- 0.03%). These data suggest that the absorption of bismuth following oral administration of bismuth sucrose octasulfate is significantly lower than that from De-Nol and similar to that from Pepto-Bismo.

Administration, Oral↗
PubMed1998

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

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.

Administration, Oral↗
PubMed1992

Comparison of plasma bismuth levels after oral dosing with basic bismuth carbonate or tripotassium dicitrato bismuthate.

In 20 healthy subjects plasma bismuth concentration was measured after single oral doses of basic bismuth carbonate or tripotassium dicitrato bismuthate. The drugs were administered in the fasted state or immediately after ingestion of a standard breakfast. After basic bismuth carbonate, plasma bismuth rose to concentrations between 0.7 and 2.6 micrograms/L in the fasted state, while after the meal the maximal level was only 1.3 micrograms/L. In contrast to these very low levels after basic bismuth carbonate, the administration of tripotassium dicitrato bismuthate was paralleled by an increase of plasma bismuth to concentrations between 15 and 232 micrograms/L with a mean peak value of 64 +/- 15.3 (S.E.M.) micrograms/L in the fasted state. Postprandial ingestion of tripotassium dicitrato bismuthate attenuated the peak concentrations to 10.9 +/- 6.3 micrograms/L. One subject, however, had a value of 120 micrograms/L. This study demonstrates that basic bismuth carbonate leads to very low plasma bismuth concentrations, which are far below the critical range that might eventually be associated with bismuth neurotoxicity. Therefore this compound can be considered potentially useful for bismuth therapy of gastrointestinal disorders.

Administration, Oral↗
PubMed1994

Comparative pharmacokinetics of bismuth from ranitidine bismuth citrate (GR122311X), a novel anti-ulcerant and tripotassium dicitrato bismuthate (TDB).

GR122311X (ranitidine bismuth citrate, Glaxo Group Research Ltd.) is a salt of ranitidine with a complex of bismuth and citric acid which is being developed for the treatment of peptic ulceration. In this study, 4 groups of 12 healthy male subjects were dosed for 10 days with either GR122311X 500 mg bid (301 mg bismuth per day), GR122311X 1.0 g bid (602 mg bismuth per day), tripotassium dicitrato bismuthate (TDB, DeNoltab, Gist Brocades Ltd., Weybridge, England) 240 mg bid (431 mg bismuth per day) or placebo. After the last dose the geometric mean for Cmax for 500 mg bid of GR122311X was 5 ng.g-1, for 1.0 g bid GR122311X it was 12 ng.g-1 and it was 21 ng.g-1 for 240 mg TDB bid. The corresponding trough plasma levels were 2 ng.g-1, 4 ng.g-1 and 4 ng.g-1, respectively. The AUC over a dosing interval after the last dose (AUC tau) were 34 ng.h.g-1, 71 ng.h.g-1 and 79 ng.h.g-1, respectively. The bismuth urinary recoveries over the last dosing interval (Ae tau) were 97 micrograms, 227 micrograms and 309 micrograms, respectively, which is less than 1% of the administered doses. The renal clearance of bismuth was less than the glomerular filtration rate. After adjustment for bismuth dose, the Cmax for GR122311X 500 mg was 35% that of TDB, while for GR122311X 1.0 g the Cmax was 42% that of TDB. Similar differences were observed for Ae tau. In conclusion bismuth pharmacokinetics after oral administration of GR1223311X exhibited lower Ae tau and Cmax, with a much narrower Cmax range than those observed for TDB.

Adolescent↗
PubMed1979

Bismuth toxicity in man - I. Bismuth blood and urine levels in patients after administration of a bismuth protein complex (Bicitropeptide).

In the course of a double-blind clinical trial of treatment involving a bismuth protein complex (Bicitropeptide), an antacid and placebo, blood samples (33 patients) and urine samples (43 patients) were collected for bismuth analysis from patients on bismuth therapy at the beginning of the trial (week 0) and at weeks 3 and 6. Base line blood (2 - 11 ng/l) and urine (2 - 29 ng/l) values were not zero and appeared to have reached "saturation" values in many cases after 3 weeks (Blood : 4 - 33 ng/l and Urine 60 - 600 ng/l). After 6 weeks, blood values were 5 - 20 ng/l and urine values 63 - 780 ng/l. It is concluded that these blood and urine levels are not associated with significant toxicity in man.

Antacids↗
PubMed1997

Mass balance of 14C-bismuth sucrose octasulfate in Sprague-Dawley rats: evidence for dissociation of bismuth from sucrose octasulfate.

The mass balance of 14C bismuth sucrose octasulfate (BISOS) was investigated in eight male Sprague-Dawley rats after single oral doses of 1.0 g kg-1. Bismuth and radioactivity were monitored in blood, urine, and feces for up to 144 h post-dose, while kidneys, brain, liver, and lungs were assayed for bismuth at 144 h post-dose. In a separate experiment, bismuth was monitored in bile of bile-duct-cannulated animals for 48 h post-dose. Fecal excretion of bismuth averaged 95.8 +/- 5.30% bismuth dose, while 99.2 +/- 3.63% of the radiolabel was excreted in feces. Urinary excretion of bismuth averaged 0.051 +/- 0.028% bismuth dose, and 1.83 +/- 1.08% radioactive dose. Biliary excretion of bismuth averaged 0.0003 +/- 0.0006% bismuth dose, and 0.026 +/- 0.030% radiolabeled dose. An average 0.005 +/- 0.002% of the bismuth dose was present in kidney, liver, and lung. Bismuth levels in brain were below quantifiable limits. Though BISOS contains 57.3% by weight of bismuth, peak blood concentrations of bismuth were three orders of magnitude lower than for BISOS equivalents (Cmax for BISOS averaged 110 +/- 55.4 micrograms eq mL-1, while for bismuth it was 26.1 +/- 10.3 ng mL-1). This data indicates that bismuth dissociates from sucrose octasulfate, probably during the absorption phase, and exhibits differential pharmacokinetic characteristics from sucrose octasulfate. The low biliary and urinary excretion of both bismuth and BISOS equivalents is indicative of low systemic absorption. Greater than 96% recovery in feces, bile, and urine indicates that mass balance was achieved following oral administration.

Absorption↗
PubMed2000

Solubility, absorption, and anti-Helicobacter pylori activity of bismuth subnitrate and colloidal bismuth subcitrate: In vitro data Do not predict In vivo efficacy.

OBJECTIVES: The aim of this study was to compare the dissolution, bioavailability, and anti-Helicobacter pylori activity of bismuth subnitrate and colloidal bismuth subcitrate. This could, first, provide insights into the mechanism of action of bismuth and, second, help to develop optimal therapeutic strategies. METHODS: Solubility and aquated size of bismuth species were determined in human gastric juice, while absorption into blood and urinary excretion of bismuth was determined in volunteers. Activity against H. pylori was determined in vitro in the presence and absence of antibiotics, while H. pylori eradication was compared in vivo. RESULTS: Bismuth from colloidal bismuth subcitrate was at least 10% soluble and ultrafilterable and was absorbed in volunteers (>0.5%), whereas that from bismuth subnitrate was insoluble and not absorbed (<0.01%). Colloidal bismuth subcitrate was active against H. pylori (mean inhibitory concentration, </=12.5 microg/ml), while bismuth subnitrate was inactive (>400 microg/ml); neither was synergistic with antibiotics. With in vivo triple therapy, bismuth subnitrate was as effective as colloidal bismuth subcitrate in eradicating H. pylori (74% and 70% eradicated, respectively). CONCLUSIONS: Colloidal bismuth subcitrate, unlike bismuth subnitrate, is partially soluble, absorbed in humans, and directly toxic to H. pylori in vitro. Surprisingly, however, these preparations had similar efficacy in vivo against H. pylori within triple therapy, suggesting that bismuth compounds may also exhibit indirect antimicrobial effects. We propose that this is an effect on the gastric mucus layer. Nonabsorbable bismuth compounds should be preferentially considered in bismuth-based therapies against H. pylori, as they would minimize toxicity while maintaining efficacy.

Anti-Bacterial Agents↗
PubMed2001

Histochemical tracing of bismuth in Helicobacter pylori after in vitro exposure to bismuth citrate.

BACKGROUND: Bismuth-containing drugs are widely used in the treatment of Helicobacter pylori associated peptic ulcer. The mechanism of action of bismuth salts is, however, not fully understood, and at present no histochemical techniques for the demonstration of bismuth in H. pylori are available. The aims were to present a histochemical method for the detection of bismuth in H. pylori and to demonstrate bismuth uptake in H. pylori after in vitro exposure to bismuth citrate. METHODS: H. pylori cultures (the strain used in this study was CCUG 17874), were exposed to bismuth citrate at different concentrations (0, 4.6, 80, 200 microM) and for different lengths of time (0 min, 15 min, 1 h, 24 h, 48 h). The samples were fixed in glutaraldehyde, centrifuged, and exposed to autometallographic (AMG) development in order to detect bismuth histochemically. RESULTS: A detailed protocol on the AMG bismuth technique on H. pylori exposed to bismuth in vitro is given. This method results in easily detectable AMG grains of silver enhanced bismuth particles at the electron microscopical level, and shows that bismuth accumulates in H. pylori, predominantly near the wall of the bacteria. Bismuth uptake is followed by bacterial degeneration. CONCLUSION: The present technique with its ability to trace bismuth constitutes a valuable tool in the efforts of clarifying the mechanism of action of bismuth on H. pylori, and supports the notion that bismuth has an antimicrobial activity in itself.

Anti-Ulcer Agents↗
PubMed1994

[Absorption and renal elimination of bismuth from 6 different bismuth salts after a single dosage].

The absorption and renal excretion of bismuth from seven pharmaceutical bismuth preparations was studied in five healthy volunteers. Following a single oral dose of colloidal bismuth subcitrate (CBS), basic bismuth salicylate (BSS), basic bismuth gallate (BSG), basic bismuth carbonate (BSC), bismuth aluminate (BA) and two different basic bismuth nitrate (BSN) preparations, ingested one hour prior to the breakfast, containing 350 mg bismuth in all but one bismuth subnitrate compound, the latter was given in a 1480 mg dose laid on granulated gum karaya, the bismuth serum concentrations (0 to 6 h) and urinary excretion (for 2 days) were measured. Slight amounts of bismuth were rapidly absorbed in all experiments with low transient mean peak concentrations between 0.6 (BSN) and 9.1 micrograms/l (CBS)--reached within 20-60 min--with a wide intra- und interindividual variability. The highest peak serum bismuth concentration was 18 micrograms/l in response to CBS. The median integrated 6-hour serum bismuth concentration after dosing with CBS and BSG was 49 and 32 ng h/ml, respectively, after dosing with BSC, BA, BSS, BSN and BSN1480 13, 11, 3, 0 and 5 ng h/ml, respectively. The values for CBS were significantly greater than after BSS and BSN350. There was a very strong overall correlation between 48-h urinary bismuth excretions and the corresponding integrated 6-hour serum bismuth concentrations (p < 0.001).

Administration, Oral↗
PubMed2000

Double-blind comparison of absorbable colloidal bismuth subcitrate and nonabsorbable bismuth subnitrate in the eradication of Helicobacter pylori and the relief of nonulcer dyspepsia.

BACKGROUND: Bismuth is widely used for the eradication of H. pylori, especially in developing countries, although there are concerns over its neurotoxicity. Whether bismuth has to be absorbed in humans to act against H. pylori is not known. In this study, we compared "absorbable" (colloidal bismuth subcitrate) and "nonabsorbable" (bismuth subnitrate) bismuth as part of triple therapy in the eradication of H. pylori. MATERIALS AND METHODS: A double-blind, randomized, placebo-controlled trial was carried out with 120 H. pylori-positive patients with nonulcer dyspepsia. Group CBS + Ab (n = 35) received colloidal bismuth subcitrate (one tablet qds), amoxicillin (500 mg qds), and metronidazole (400 mg tds). Group BSN + Ab (n = 35) received bismuth subnitrate (two tablets tds) and the same antibiotics. Group Ab (n = 35) received placebo bismuth (two tablets tds) and the antibiotics. Group BSN (n = 15) received bismuth subnitrate (two tablets tds) and placebo antibiotics. Bismuth was taken for 4 weeks and the antibiotics for the first 2 weeks. H. pylori eradication, side effects, compliance, pre- and post-treatment symptom scores, and bismuth absorption were assessed. RESULTS: H. pylori eradication was 69%, 83%, 31%, and 0% in CBS + Ab, BSN + Ab, Ab, and BSN, respectively. Side effects, compliance, and symptom relief were similar in all groups, but blood bismuth levels were significantly greater in CBS + Ab than the other three groups. CONCLUSION: The efficacy of bismuth-based therapies as part of triple therapy in the eradication of H. pylori is unrelated to absorption. Hence, the use of effective but poorly absorbed bismuth preparations should be encouraged for bismuth-based eradication therapies.

Adolescent↗
PubMed1989

The absorption of bismuth from oral doses of tripotassium dicitrato bismuthate.

Two studies measured plasma concentrations of bismuth during dosing with tripotassium dicitrato bismuthate (De-Noltab). The first study compared 24 h plasma bismuth concentration and urinary bismuth excretion in six patients who had already received 29-131 days (median 47 days) of treatment with De-Noltab 2 b.d., and six healthy subjects who only received De-Noltab 2 b.d. on the day of study. There was a prompt rise in plasma bismuth concentration after each dose of De-Noltabs. The median 24 h integrated plasma bismuth concentration was similar in both groups, but the median 24 h urinary bismuth excretion was 5.4-fold higher in the patients. The second study compared the plasma bismuth concentrations after the first and third doses of De-Noltab 2 b.d. in 16 healthy subjects. The median peak bismuth concentration occurred 30 min (range 15-105 min) post-dosing. The peak plasma bismuth concentration was greater than 50 ng/ml in 14 of the 16 subjects, and greater than 100 ng/ml in nine of the subjects. There was no significant difference in the median integrated 10-h plasma bismuth concentration after the first or third dose of De-Noltabs. The results of these studies confirm that bismuth is absorbed and sequestrated during dosing with De-Noltabs. Bismuth is absorbed rapidly after oral dosing with De-Noltabs, to produce peak plasma bismuth concentrations hitherto considered to be in the range associated with bismuth neurotoxicity.

Administration, Oral↗
PubMedDate not supplied

Uptake of bismuth in motor neurons of mice after single oral doses of bismuth compounds.

Bismuth, a component of many gastrointestinal medications, is a heavy metal little studied as regards nervous system uptake. We were interested to see if low doses of intragastric bismuth entered the nervous system, and if dietary selenium influenced the amount of bismuth detected. Mice were given 40 to 1200 mg/kg of bismuth subnitrate (BSN), bismuth subsalicylate (BSS), colloidal bismuth subcitrate (CBS), or ranitidine bismuth citrate (RBC) intragastrically. Mice on low- or high-selenium diets were given 4 to 32 mg/kg of bismuth from RBC. One week later, sections of nervous tissue were stained with autometallography to detect bismuth grains (Bi(AMG)). Bismuth was found in neurons with axons outside of the nervous system, in particular motor neurons, and in cells outside the blood-brain barrier. The lowest bismuth dose which resulted in Bi(AMG) in motor neurons was 696 mg/kg from BSN, 57 mg/kg from BSS, 29 mg/kg from CBS, and 26 mg/kg from RBC. No bismuth was seen in motor neurons of mice on the low-selenium diet. Intragastric doses of bismuth therefore enter mouse motor neurons, and the amount detectable varies with dietary selenium.

Administration, Oral↗
PubMed1995

Gastric persorption of bismuth from ranitidine bismuth citrate.

AIM: To determine whether bismuth penetrates the gastric mucosa after dosing with ranitidine bismuth citrate. METHODS: Twelve patients presenting with dyspepsia were randomized to receive either ranitidine bismuth citrate or placebo, 20-40 min prior to endoscopy. Biopsies were taken from four sites during endoscopy: the first and second parts of the duodenum, the antrum, and the body of the stomach. Biopsies were analysed by electron microscopy and X-ray microanalysis. RESULTS: Bismuth particles were found to be interposed between epithelial cells in the antral mucosa of three of eight patients who were dosed with ranitidine bismuth citrate. Columns of bismuth particles could be tracked down the lamina propria and were seen to be surrounding blood vessels. Bismuth particles were observed in the inter- and intra-cellular channels of the endothelial cells of the blood vessels in the lamina propria and also close to the luminal surface of the endothelial cell. This process of persorption was similar to that described in a previous report of electron microscopy appearances of the gastric antrum after dosing with tripotassium dicitrato bismuthate, but was quantifiably smaller and not observed in all the patients dosed with ranitidine bismuth citrate. No penetration of the mucosa by bismuth particles was seen in the body of the stomach or the duodenum. CONCLUSION: Penetration of bismuth particles into the gastric mucosa may occur after oral dosing with ranitidine bismuth citrate.

Adult↗
PubMed1996

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

1. The pharmacokinetics of bismuth and ranitidine derived from oral doses of ranitidine bismuth citrate 800 mg given twice daily for 28 days were examined in this double-blind, placebo-controlled, parallel-group study in 27 healthy subjects. 2. Bismuth accumulation in plasma reflected its multicompartmental disposition, achieving the majority of predicted steady state within 14-28 days. Bismuth absorption from ranitidine bismuth citrate is limited (< 0.5% of the dose), and bismuth elimination is predominantly renal secretion. Peak plasma concentrations did not exceed 19 ng ml-1, remaining well below those associated with bismuth toxicity. Bismuth was measurable at low concentrations in plasma and urine for up to 5 months after the last dose. Plasma bismuth concentration-time data and urinary excretion data were best described by separate multicompartmental models, with terminal half-lives averaging 21 days and 45 days, respectively. 3. The pharmacokinetics of ranitidine derived from ranitidine bismuth citrate were similar to those of ranitidine administered alone. Ranitidine did not appreciably accumulate in plasma. 4. Ranitidine bismuth citrate was well-tolerated during 28 days of repeated dosing.

Adult↗
PubMed1991

Tripotassium dicitrato bismuthate: absorption and urinary excretion of bismuth in patients with normal and impaired renal function.

We have investigated the absorption and urinary excretion of tripotassium dicitrato bismuthate during a treatment course of 4 weeks in 7 patients with normal renal function (creatinine clearance 115 +/- 29 ml/min; mean +/- S.D.), in 7 patients with impaired renal function (creatinine clearance = 34 +/- 19 ml/min) and in 4 dialysed patients. Following the first dose of tripotassium dicitrato bismuthate (216 mg bismuth b.d.), and after 2 and 4 weeks of treatment (dialysed patients received only 108 mg/b.d.), plasma and urine concentrations of bismuth were monitored for 2 and 24 h, respectively. After stopping therapy plasma and urine concentrations of bismuth were followed for 4 and 6 weeks, respectively. In all three groups of patients small amounts of bismuth (mean values 0.26 to 0.28% of dose) were rapidly (transient mean peak concentrations between 40 and 134 micrograms/L) reached within about 30 to 40 min, absorbed and plasma levels demonstrated a wide intra- and inter-individual variability. Absorption profiles were not altered during the treatment course; however, the trough plasma concentration of bismuth demonstrated an about 3- to 5-fold accumulation (correlated to creatinine clearance) from about 5 micrograms/L to 15 micrograms/L (normal renal function) or to 20-25 micrograms/L (impaired renal function). Pre-study bismuth levels could be detected within 2 to 4 weeks after stopping therapy in all subjects whereas urinary concentrations were still elevated 6 weeks after the course of treatment. Our results indicate that tripotassium dicitrato bismuthate is absorbed in very low amounts during standard therapy. However, dependent on renal function, accumulation to non-toxic levels does occur during a course of treatment. It appears prudent to halve tripotassium dicitrato bismuthate dosage in patients with severe renal insufficiency (creatinine clearance less than or equal to 20 ml/min) to avoid any possible toxic risks. In such patients monitoring of the plasma bismuth concentration might be helpful, especially if longer or repeated treatment is anticipated.

Absorption↗
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↗