Hemofiltrability of histamine H2-receptor antagonist, nizatidine, and its metabolites in patients with renal failure.
To study if an H2-receptor antagonist, nizatidine, and its metabolites [N-2-monodesmethylnizatidine (N-2-MDMN) and nizatidine sulfoxide (nizatidine S-Ox)] would be removed by an arteriovenous hemofiltration, the authors measured their plasma concentrations and amounts recovered in ultrafiltrate during 11 sessions of an intermittent hemofiltration performed in seven patients with renal failure who were given an oral administration of nizatidine (150 mg). The concentrations of the parent drug and its metabolites in plasma and ultrafiltrate were determined with a high-performance liquid chromatography with ultraviolet absorbance detection. The mean (+/- standard deviation [SD]) amounts of nizatidine removed by the procedure performed at the mean ultrafiltration rate of 18 (range, 11-25) mL/min over the mean duration of 179 (60 to 300) minutes accounted for 1.9 +/- 1.4% of the dose administered. The corresponding values for N-2-MDMN and nizatidine S-Ox were 0.3 +/- 0.2% and 0.2 +/- 0.2% of the molar dose of nizatidine, respectively. There was a significant correlation between the filtration rate and the hemofiltration clearance of nizatidine (r = .94, P < .001) or its active metabolite, N-2-MDMN (r = 0.83, P < .01), indicating that the sieving coefficient (Sc), an index of filtration efficiency, for these compounds is largely constant (0.59 and 0.67 for nizatidine and N-2-MDMN, respectively) under the current hemofiltration conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Saima
S
S
Division of Nephrology, National Medical Center, Tokyo, Japan.
Echizen
H
H
Yoshimoto
K
K
Ishizaki
T
T
D000328:Adult; D000368:Aged; D005260:Female; D006440:Hemofiltration; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016567:Nizatidine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*
C066300:nizatidine sulfoxide; C066301:N-desmethylnizatidine; D016567:Nizatidine