Chemistry Reference
In-Depth Information
have been reported by Wieriks
et al
. (1982), who found
that the kidneys of both dogs and rats had the highest
visceral concentrations of bismuth after 6 or 3 months,
respectively. In the rat, the cecum also showed exten-
sive bismuth accumulation. Pharmacokinetic studies in
animals (Pieri and Wegmann, 1981) using
205
Bi-citrate
have demonstrated a two-compartment model that also
demonstrated high levels in the kidney and medulla
of the brain. Bismuth has been found to bind to trans-
ferrin in serum but in a noncanonical manner or more
open manner that confers a lower affi nity than iron or
indium for this protein, which may explain the rela-
tively low effi ciency of bismuth delivery to cells after
administration of bismuth-containing pharmaceuticals
(Miquel
et al
., 2004; Sun and Szeto, 2003; Zhang
et al
.,
2004). Canena
et al
. (1998) studied the distribution of bis-
muth in rats treated with ranitidine bismuth citrate and
bismuth subcitrate for 15 days with a twice per day oral
gavage. Rats given bismuth subcitrate alone at a dose
of 13.7
5.3 Excretion
Ingested bismuth is largely eliminated unabsorbed
in feces. Model values for the daily balance of bismuth
in a reference manual are dietary intake 20
µ
g
;
fecal
elimination 18
µ
g
;
and urinary excretion 1.6
µ
g (Soll-
man
et al
., 1938).
Absorbed bismuth is mainly excreted in urine,
although the biliary/fecal excretion of bismuth as
reported by Pieri and Wegmann (1981). The rate of
excretion of bismuth after intramuscular injection into
rabbits of 13 different compounds was studied by
Kolmer
et al
. (1939). Water-soluble compounds were
excreted more rapidly than those suspended or dis-
solved in oil. Excretion in 4 days varied from 82.2% of
the dose for aqueous solution of bismuth thioglycol-
late to 1.9% for oil suspension of bismuth oleate, but
the excretion continued for at least 36 days. Durbin
(1960) compared the excretion of elements of group
V in rats after intramuscular injection of soluble com-
pounds in oxidation state +3. The metabolism of radio
bismuth closely resembled the metabolism of UO22+,
suggesting that Bi(III) was oxygenated or in a “basic”
form. The retention in the kidney was short, and by
the 17th day after injection, 95% of the dose had been
excreted.
The permeability of the placenta to bismuth was
demonstrated by Leonard and Love (1928) after intra-
muscular injection of potassium bismuth tartrate and
sodium potassium tartro-bismuthate into pregnant
rabbits and cats.
g/kg showed marked uptake in a number of
tissues with highest concentrations in the kidney. Rats
given the ranitidine bismuth subcitrate at a dose of dose
of 22.8
µ
g/kg showed markedly lower kidney bismuth
concentrations and undetectable levels of bismuth in the
brain. The intracellular binding of bismuth in the kid-
ney has been studied (Piotrowski and Szymanska, 1976;
Szymanska and Piotrowski, 1980; Szymanska and Zela-
zowski, 1979a) with respect to low molecular-weight
bismuth-binding proteins that seemed to have some
properties distinct from metallothionein. More recent
studies (Boogaard
et al
., 1991; Kaji
et al
., 1994; Naga-
numa and Imura, 1994; Palmiter, 1994; Szymanska
et al
.,
1993; Zindenberg-Cherr
et al
., 1989) have shown bis-
muth to be an effective inducer of metallothionein and
to bind to this protein. This knowledge has been applied
to protecting against the nephrotoxicity of anticancer
drugs such as cisplatin (Imura
et al
., 1987; Kondo
et al
.,
1991, 2004; Leussink
et al
., 2003) and Adriamycin (Satoh
et al
., 2000). These investigators observed, in tumor-
bearing mice and patients with renal cell carcinoma,
that orally administered bismuth was transported to
normal tissues and not cancerous tissues. In addition,
bismuth induction of metallothionein has been linked
to the attenuation of the teratogenic effects of cadmium
in mice (Naruse and Haysashi, 1989) and the adverse
effects of gamma irradiation on the bone marrows of
mice (Satoh
et al
., 1989).
The autopsy distribution of bismuth in 22 patients
who received therapeutic intramuscular injections
(mainly bismuth salicylate) was as follows (median
values,
µ
5.4 Biological Half-Times
ICRP (1960) adopted the following model values
for the biological half-times of bismuth in man: whole-
body retention, 5 days; kidney, 6 days; liver, 15 days;
spleen, 10 days; and bone, 13.3 days. Slikkerveer and
deWolff (1989) reported that the elimination of bismuth
from blood displayed multicompartmental kinetics in
humans from 3.5 minutes to up to 17-22 years.
6 BIOLOGICAL MONITORING
The concentrations of bismuth in healthy human
tissue in the United Kingdom have been reported by
Hamilton
et al
. (1972; 1973) using SSMS. The highest
mean concentration (400
g/kg wet weight) was found
in the kidney, followed by the bone (<200
µ
g/kg). The
brain, lung, and lymph nodes contained bismuth in
concentrations from 10-40
µ
g/kg, wet weight): kidney. 33.3; liver. 6.8;
spleen. 1.6; colon. 1.3; lung. 0.9; brain. 0.6; and blood.
0.5 (Sollman
et al
., 1938).
µ
µ
g/kg. Concentrations in
the range from 2-8
µ
g/kg were found in the testis,
