Pharmacokinetics of famotidine in normal subjects and in patients with chronic liver disease.
The pharmacokinetics of famotidine were studied in seven healthy control subjects and in 14 patients with cirrhosis, following single oral and intravenous 20-mg dose administration, and after seven daily doses of 40 mg. Following intravenous (i.v.) administration, the mean (range) total plasma clearance values were not significantly different in the patients with compensated cirrhosis (n = 7), 337 (241-576) ml/min or in the patients with decompensated cirrhosis (n = 7), 270 (120-408) ml/min compared with the control group, 370 (154-612) ml/min. The mean half-life in the compensated cirrhotics, 2.86 (1.87-4.98) h, was similar to that in the control group 2.91 (1.86-6.03) h, but it was insignificantly prolonged in the decompensated cirrhotics 3.35 (2.00-5.77) h. The mean, maximum, plasma famotidine concentrations after single oral doses were comparable between the groups but there was considerable inter-subject variability, with individual values ranging from 17 to 139 ng/ml. Peak plasma concentrations were reached within 2-3 h, although more variability was observed among patients with decompensated cirrhosis. The mean systemic availability of the drug, estimated from urinary recovery, was 0.39 (0.15-0.64) in the healthy controls, 0.35 (0.14-0.51) in the patients with compensated cirrhosis and 0.38 (0.13-0.77) in the patients with decompensated cirrhosis. No significant increases were observed in plasma trough famotidine concentrations following multiple oral dosing in any of the subjects, and the kinetic variables after the seventh dose were not significantly different from those following the single oral dose. No significant changes were observed in psychometric performance in control subjects or in patients between the pre-study day and day seven of the multiple oral dose phase.
Morgan
M Y
MY
Academic Department of Medicine, Royal Free Hospital, UK.
Stambuk
D
D
Cottrell
J
J
Mann
S G
SG
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D015738:Famotidine / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011597:Psychomotor Performance / Q000187:drug effects
D015738:Famotidine