Hemofiltrability of H2-receptor antagonist, famotidine, in renal failure patients.
To determine if a new H2-receptor antagonist, famotidine, would be significantly removed by arteriovenous hemofiltration, we measured plasma concentrations and amounts of the drug recovered in ultrafiltrate during 18 sessions of an intermittent hemofiltration performed in five patients with renal failure receiving the repeated intravenous dosings of the drug (5-20 mg/day). Plasma and ultrafiltrate drug concentrations were determined by using a high performance liquid chromatography with fluorescent detection. The mean (+/- SD) amount of the drug removed by the procedure, which was performed at the mean ultrafiltration rate of 19.0 +/- 6.0 ml/min over the mean duration of 212 +/- 168 min, corresponded to 4.1 +/- 2.2% of the daily maintenance doses. There was a significant (r = 0.90, P less than .01) linear relationship between the hemofiltration clearance and the ultrafiltration rate, indicating that the sieving coefficient, an index filtration efficiency, for the drug was largely constant (i.e., 0.73 +/- 0.10) over the ranging filtration rates (i.e., 3.9-29.5 mL/min) employed in the present study. When the mean filtration efficiency of 0.73 obtained from the study is extrapolated into a 24-hour continuous arteriovenous hemofiltration performed at commonly used filtration rates (i.e., 6-12 ml/min), the 24-hour hemofiltration clearances are estimated to range from 4 to 9 ml/min. These clearance values are found to correspond to only 10 to 25% of the mean total body clearance (about 35 ml/min) reported from anuric patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Saima
S
S
Division of Cardiology, National Medical Center, Tokyo, Japan.
Echizen
H
H
Yoshimoto
K
K
Ishizaki
T
T
D000368:Aged; D000369:Aged, 80 and over; D002851:Chromatography, High Pressure Liquid; D015738:Famotidine / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D005260:Female; D006207:Half-Life; D006440:Hemofiltration; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D014462:Ultrafiltration
D015738:Famotidine