Lf. Lacey et al., COMPARATIVE PHARMACOKINETICS OF BISMUTH FROM RANITIDINE BISMUTH CITRATE (GR122311X), A NOVEL ANTI-ULCERANT AND TRIPOTASSIUM DICITRATO BISMUTHATE (TDB), European Journal of Clinical Pharmacology, 47(2), 1994, pp. 177-180
GR122311X (ranitidine bismuth citrate, Glare 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 eit
her GR122311X 500 mg bid (301 mg bismuth per day), GR122311X 1.0 g bid
(602 mg bismuth per day), tripotassium dicitrato bismuthate (TDB, DeN
oltab, Gist Brocades Ltd., Weybridge, England) 240 mg bid (431 mg bism
uth per day) or placebo. After the last dose the geometric mean for C-
max for 500 mg bid of GR122311X was 5 ng.g(-1), for 1.0 g bid GR122311
X it was 12 ng.g(-1) and it was 21 ng.g(-1) for 240 mg TDB bid. The co
rresponding 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 dos
e (AUC(tau)) were 34 ng.h.g(-1), 71 ng.h.g(-1) and 79 ng.h.g(-1), resp
ectively. The bismuth urinary recoveries over the last dosing interval
(Ae(tau)) were 97 mu g, 227 mu g and 309 mu g, respectively, which is
less than 1% of the administered doses. The renal clearance of bismut
h was less than the glomerular filtration rate. After adjustment for b
ismuth dose, the C-max for GR122311X 500 mg was 35% that of TDB, while
for GR122311X 1.0 g the C-max was 42% that of TDB. Similar difference
s were observed for Ae(tau). In conclusion bismuth pharmacokinetics af
ter oral administration of GR1223311X exhibited lower Ae(tau) and C-ma
x, with a much narrower C-max range than those observed for TDB.