Excretion bismuth

Rates of bismuth excretion after intramuscular injection into rabbits were monitored for 13 different bismuth compounds, and water-soluble compounds were seen to be excreted more rapidly than those suspended or dissolved in oil. Excretion of bismuth during 4 days ranged from 82.2% of the dose for an aqueous solution of bismuth thioglycollate to 1.9% for an oil suspension of bismuth oleate, though excretion contin-... 

Two bismuth compounds are available bismuth subsalicylate, a nonprescription formulation containing bismuth and salicylate, and bismuth subcitrate potassium. In the USA, bismuth subcitrate is available only as a combination prescription product that also contains metronidazole and tetracycline for the treatment of H pylori. Bismuth subsalicylate undergoes rapid dissociation within the stomach, allowing absorption of salicylate. Over 99% of the bismuth appears in the stool. Although minimal (< 1%), bismuth is absorbed it is stored in many tissues and has slow renal excretion. Salicylate (like aspirin) is readily absorbed and excreted in the urine. 

There have been no fatalities in industry attributed to bismuth and it is regarded as relatively non-toxic for a heavy metal.246 The toxic problems which have been recorded have in the main been iatrogenic illnesses. A characteristic blue-black line on the gums, the bismuth line , which may persist for years, is a feature of bismuth overdosage. Soluble salts are excreted via urine and may cause mild kidney damage. Less soluble salts may be excreted in the faeces, which may be black in colour due to the presence of bismuth sulfide. Table 31 contains some toxicity data. 

Adverse effects. Bismuth chelate, particularly as a liquid formulation, darkens the tongue, teeth and stool the effect is less likely with the tablet, which is thus more acceptable. There is little systemic absorption of bismuth from the chelated preparation, but bismuth is excreted by the kidney and it is prudent to avoid giving the drug to patients with impaired renal fimction. Urinary elimination continues for months after bismuth is discontinued. 

Gregus and Klaassen carried out a comparative study of fecal and urinary excretion and tissue distribution of eighteen metals in rats after intravenous injection. Total (fecal + urinary) excretion was relatively rapid (over 50% of the dose in 4 days) for cobalt, silver and manganese between 50 and 20% for copper, thallium, bismuth, lead, cesium, gold, zinc, mercury, selenium and chromium and below 20% for arsenic, cadmium, iron, methylmercury and tin. Feces was the predominant route of excretion for silver, manganese, copper, thallium, lead, zinc, cadmium, iron and methylmercury whereas urine was the predominant route of excretion of cobalt, cesium, gold, selenium, arsenic and tin. Most of the metals reached the highest concentration in liver and kidney. However, there was no... 

Bismuth is predominantly excreted via the kidney and would be expected to accumulate in patients with renal insufficiency. It is not impossible that combined exposure to bismuth and other metals could render the patient more susceptible to bismuth toxicity the parallels between the complications seen here and with other light metals (zinc, aluminium) are striking. 

In humans, the absorption of the heavy metal bismuth is negligible (<1%) but salicylate is absorbed readily (Nwokolo et al 1990), with as much as 95% of the administered dose excreted in urine. No data are available on the degree and consequence of absorption of bismuth or salicylate in horses. 

It is fascinating to note the recent re-awakening of interest in bismuth therapies since the discovery in 1982 that the intestinal bacterium Helicobacter pylori may well initiate ulcer formation by excreting acid. Bismuth, in common with many heavy metals, is bactericidal and so the lasting effects of bismuth citrate therapy may well be a combination of ulcer healing (from the precipitates) as well as ulceration initiator suppression (from the bacteriocidal action). In vitro the organism is sensitive to bismuth but results in vivo are feeble. However, combinations of bismuth with antibiotics such as amoxicillin or tetracycline have success rates of 80%, i.e. four times the 20% success rate described above. 

Oral fluid and electrolyte replacement is the cornerstone of treatment. Oral Lactobacillus therapy may reduce the duration of diarrhea and of viral excretion. There is no role for antibiotics in acute infection. Bismuth subsalicylate, although shown to decrease the duration of diarrhea and stool outpuf is not recommended for routine use because of the self-Umiting nature of the disease and the risk of bismuth subsalicylate overdose. AntimotUity agents are not recommended because they have not been shown to decrease the duration or volume of diarrhea. 

Bismuth levels in land animals were generally below 4-20pgkg and in marine animals and mammalian blood were considerably lower (< 40 to 300 pgkg DW and 10 pgkg respectively) (Fowler and Vouk 1986, Thomas et al. 1988, Thomas 1991). In man, small amounts of bismuth are excreted in the urine, indicating some gastrointestinal absorption, and small amounts are also detected in the blood (see Table 5.2) (Thomas 1991). 

There exist no reliable criteria to define Bi absorption, but possible criteria are blood and plasma levels or daily urinary excretion. Blood levels of Bi > 300 pg L are diminished by hemodialysis in vitro, and this may be explained by there being two different forms of bismuth, namely soluble and bound (Allain 1976). Monitoring of Bi treatments should also include the determination of Bi in whole blood as well as in plasma (Rao and Feldman 1990). Bismuth administered subcutaneously to rats as BiClj is deposited in the kidneys, which were found to contain > 50% of the accessible pool of bismuth. Retention in the kidneys was diminished, while levels in liver and 12 other tissues were augmented (Jad-wiga et al. 1979). 

Bismuth ingested from therapeutic agents is mainly eliminated in the feces as bismuth sulfide. In general, 10-20% is excreted within 5 days, but elimination is still incomplete after 10 days (Iffland... 

Tab. 5.3 Blood concentrations, urinary excretion and renal clearance of bismuth in asymptomatic patients and in those with neurotoxicity after ingestion of bismuth salts...

Burns R, Thomas DW and Baron VJ (1974) Reversible encephalopathy possible associate with bismuth subgallate ingestion. Br Med J 1 220—223. Chaleil D and Aliain P (1980) Effect of oral administration of bismuth subnitrate on distribution and excretion of intrapcritoneally given radiobismuth in rats. Ann Pharm Fr 37 285-290. Chattopadhyay A and Jervis RE (1974) Multielement determination in market-garden soils by instrumental photon activation analysis. Anal Chem 46(12) 1630-1639. 

Lee SP (1981) Studies on the absorption and excretion of tripotassium dicitrato-bismuthate in man. Res Commun Chem Pathol Pharmacol 34(2) 359-364. 

Paul and coworkers (1989) have investigated the antidotal actions of several compounds on the acute toxicity of selenium in rats. Male Wistar rats were injected sodium [ Sejselenite subcutaneously in this study. Intraperitoneal administration of diethyldithiocarbamate or treatment with citrate salt of bismuth, antimony, or germanium, administered subcutaneously, reduced selenium-induced loss of body weight in the animals. Germanium citrate and bis(carboxyethyl)germanium sesquiox-ide promoted increases in the 24-hour urinary excretion of selenium when administered 15 minutes after sodium selenite. 

B. Because renal excretion is the predominant route of elimination of unithiol and its metal complexes, caution is warranted in administering unithiol to patients with severe renal insufficiency. Use of unithiol as an adjunct to hemodialysis or hemofiltration in patients with anuric renal failure due to mercury salts and bismuth has been reported. 

The daily elimination in untreated people is estimated at 12 ixg [12] including 2.9 xg excreted with the urine [27]. Ingested bismuth from therapeutics is mainly eliminated with feces as sulfide. Within 5 days 10-20% is excreted. But elimination is not finished after 10 days. Overall 99% may be eliminated in this way [3,12,17,29]. Absorbed bismuth is mainly excreted by urine the biliary/fecal elimination route is only about half of the urinary one [3,6,62-64]. Half-lives in blood after a single dose or during a treatment depend on the kind of the Bi compound, the amounts ingested, and the blood levels. Elimination from blood of bismuth subcitrate is biphasic [17,28,65]. In cases of encephalopathy with remarkably high urine and blood levels (2000 and 1500 p-g/liter, respectively), half-lives were calculated for urine (4.5 days) and blood (5.2 days). Liquor levels decreased more slowly with a half-life of 15.9 days [53]. Elimination kinetics is also described as a three-compartment model with half-lives of 3.5 min, 0.25 hr, and 3.2 hr [6]. Biological half-times in humans are reported for the whole body 5 days, the kidney 6 days, and the liver 15 days (cited in [3]). 

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