Famotidine pharmacokinetics and molecular data

Pharmacokinetic data
Adult patients Pediatric patients
 * GI effects
 * Other effects
 * Adult pharmacokinetics
 * Pediatric pharmacokinetics
 * Pediatric pharmacodynamics

GI effects
Famotidine is a competitive inhibitor of histamine H2-receptors. The primary clinically important pharmacologic activity of Famotidine is inhibition of gastric secretion. Both the acid concentration and volume of gastric secretion are suppressed by Famotidine, while changes in pepsin secretion are proportional to volume output. In normal volunteers and hypersecretors, Famotidine inhibited basal and nocturnal gastric secretion, as well as secretion stimulated by food and pentagastrin. After oral administration, the onset of the antisecretory effect occurred within one hour; the maximum effect was dose-dependent, occurring within one to three hours. Duration of inhibition of secretion by doses of 20 and 40 mg was 10 to 12 hours. Single evening oral doses of 20 and 40 mg inhibited basal and nocturnal acid secretion in all subjects; mean nocturnal gastric acid secretion was inhibited by 86% and 94%, respectively, for a period of at least 10 hours. The same doses given in the morning suppressed food-stimulated acid secretion in all subjects. The mean suppression was 76% and 84%, respectively, 3 to 5 hours after administration, and 25% and 30%, respectively, 8 to 10 hours after administration. In some subjects who received the 20 mg dose, however, the antisecretory effect was dissipated within 6 to 8 hours. There was no cumulative effect with repeated doses. The nocturnal intragastric pH was raised by evening doses of 20 and 40 mg of Famotidine to mean values of 5.0 and 6.4, respectively. When Famotidine was given after breakfast, the basal daytime interdigestive pH at 3 and 8 hours after 20 or 40 mg of Famotidine was raised to about 5. Famotidine had little or no effect on fasting or postprandial serum gastrin levels. Gastric emptying and exocrine pancreatic function were not affected by Famotidine. Return to top

Other effects
Systemic effects of Famotidine in the CNS, cardiovascular, respiratory or endocrine systems were not noted in clinical pharmacology studies. Also, no antiandrogenic effects were noted. Serum hormone levels, including prolactin, cortisol, thyroxine (T4), and testosterone, were not altered after treatment with Famotidine. Return to top

Adult pharmacokinetics
Famotidine is incompletely absorbed. The bioavailability of oral doses is 40 to 45%. Famotidine tablets, Famotidine for oral suspension and Famotidine orally disintegrating tablets are bioequivalent. Bioavailability may be slightly increased by food, or slightly decreased by antacids; however, these effects are of no clinical consequence. Famotidine undergoes minimal first-pass metabolism. After oral doses, peak plasma levels occur in 1 to 3 hours. Plasma levels after multiple doses are similar to those after single doses. Fifteen to 20% of Famotidine in plasma is protein bound. Famotidine has an elimination half-life of 2.5 to 3.5 hours. Famotidine is eliminated by renal (65 to 70%) and metabolic (30 to 35%) routes. Renal clearance is 250 to 450 mL/min, indicating some tubular excretion. Twenty-five to 30% of an oral dose and 65 to 70% of an intravenous dose are recovered in the urine as unchanged compound. The only metabolite identified in man is the S-oxide. There is a close relationship between creatinine clearance values and the elimination half-life of Famotidine. In patients with severe renal insufficiency, i.e., creatinine clearance less than 10 mL/min, the elimination half-life of Famotidine may exceed 20 hours and adjustment of dose or dosing intervals in moderate and severe renal insufficiency may be necessary. In elderly patients, there are no clinically significant age-related changes in the pharmacokinetics of Famotidine. However, in elderly patients with decreased renal function, the clearance of the drug may be decreased. Return to top

Pediatric pharmacokinetics
Plasma clearance is reduced and elimination half-life is prolonged in pediatric patients 0 to 3 months of age compared to older pediatric patients. The pharmacokinetic parameters for pediatric patients, ages >3 months to 15 years, are comparable to those obtained for adults. Bioavailability studies of 8 pediatric patients (11 to 15 years of age) showed a mean oral bioavailability of 0.5 compared to adult values of 0.42 to 0.49. Oral doses of 0.5 mg/kg achieved AUCs of 645 ± 249 ng-hr/mL and 580 ± 60 ng-hr/mL in pediatric patients <1 year of age (N = 5) and in pediatric patients 11 to 15 years of age, respectively, compared to 482 ± 181 ng-hr/mL in adults treated with 40 mg orally. Return to top

Pediatric pharmacodynamics
Pharmacodynamics of Famotidine were evaluated in 5 pediatric patients 2 to 13 years of age using the sigmoid Emax model. These data suggest that the relationship between serum concentration of Famotidine and gastric acid suppression is similar to that observed in one study of adults. Five published studies examined the effect of Famotidine on gastric pH and duration of acid suppression in pediatric patients. The duration of effect of Famotidine I.V. 0.5 mg/kg on gastric pH and acid suppression was shown in one study to be longer in pediatric patients <1 month of age than in older pediatric patients. This longer duration of gastric acid suppression is consistent with the decreased clearance in pediatric patients <3 months of age. Return to top