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.
Treiber
G
G
Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, FRG.
Gladziwa
U
U
Ittel
T H
TH
Walker
S
S
Schweinsberg
F
F
Klotz
U
U
D000042:Absorption; D000328:Adult; D000368:Aged; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics*; D001729:Bismuth / Q000652:urine*; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism* / Q000652:urine; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D011446:Prospective Studies; D012016:Reference Values
D000897:Anti-Ulcer Agents; D009942:Organometallic Compounds; C002791:bismuth tripotassium dicitrate; D001729:Bismuth