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.
Division of Clinical Pharmacology, Glaxo Group Research Ltd., Greenford, Middlesex, UK.
L F
LF
Lacey
N M
NM
Frazer
O N
ON
Keene
J T
JT
Smith
D000293:Adolescent; D000328:Adult; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001729:Bismuth / Q000097:blood / Q000493:pharmacokinetics*; D002951:Citrates / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004311:Double-Blind Method; D004381:Duodenal Ulcer / Q000097:blood / Q000188:drug therapy*; D006635:Histamine H2 Antagonists / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011899:Ranitidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000897:Anti-Ulcer Agents; D002951:Citrates; D006635:Histamine H2 Antagonists; D009942:Organometallic Compounds; C073340:ranitidine bismuth citrate; D011899:Ranitidine; C002791:bismuth tripotassium dicitrate; D001729:Bismuth