H2Bloc Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Famotidine is a histamine receptor blocking agent which competitively inhibits the action of histamine on the H₂ receptors of parietal cells. The primary pharmacologic activity of famotidine is inhibition of gastric juice secretion. Both the acid concentration and volume of gastric secretion are suppressed by famotidine, while changes in pepsin secretion are proportional to volume output. Famotidine inhibited basal and nocturnal gastric secretion, as well as secretion stimulated by food and pentagastrin.
Pharmacokinetics: Famotidine is incompletely absorbed, with an oral bioavailability of 40 to 50%. Food may slightly enhance and antacids may slightly decrease the bioavailability of famotidine, but these alterations do not appear to be clinically significant. After oral doses, peak plasma levels occur in 1 to 3 hours. Plasma levels after multiple doses are similar to those after single doses.
After intravenous (IV) injection of a single 20 mg dose of famotidine, peak plasma concentrations of 272 ng/mL occur within 20 minutes and decrease to 163, 98, 64, 25, and 11 ng/mL at 1, 2, 4, 8, and 12 hours, respectively, after the dose.
After IV administration, inhibition of gastric acid secretion is apparent within one hour and peak inhibition occurs within 0.5 to 3 hours or 1 to 4 hours following IV or oral administration, respectively. The duration of inhibition of nocturnal gastric acid secretion is 10 to 15 hours. In a study in healthy individuals who were hypersecretors of gastric acid (basal gastric acid output of 5 or more mEq/hour), maximal inhibition of gastric acid secretion was 97.4, 99.7, or 99.4%, 2 to 4 hours and 73.8, 77.2, or 83.3%, 12 hours following a single famotidine dose of 10 or 20 mg IV or 20 mg orally, respectively.
The apparent volume of distribution of the drug is 1.1 to 1.4 L/kg in adults and does not appear to be altered substantially in patients with renal dysfunction. In children 1 to 15 years old, a volume of distribution of 1.5 to 2.07 L/kg has been reported. The drug is 15 to 20% protein bound.
Famotidine is metabolized in the liver to famotidine S-oxide (S-famotidine). The metabolite does not appear to inhibit gastric acid secretion. Orally administered famotidine undergoes minimal first pass metabolism in the liver.
The elimination half-life of famotidine averages 2.5 to 4 hours in adults with normal renal function. An elimination half-life of 2.3 to 3.38 hours has been reported in children 1 to 15 years old.
The elimination of famotidine does not appear to be affected substantially by age in adults, but is prolonged in patients with renal impairment; adjustment of dosage or dosing interval may be necessary to avoid excess accumulation of the drug in patients with moderate to severe renal impairment. In adults with creatinine clearances of 10 mL or less per minute, the elimination half-life of the drug may exceed 20 hours, with an elimination half-life of about 24 hours in anuric patients. In adults with normal renal function and those with creatinine clearances of 60 to 90, 30 to 60, or less than 30 mL/minute per 1.48 m2, the plasma half-life in the distribution phase was not affected substantially by renal function, averaging 0.18, 0.23, 0.25, or 0.24 hours, respectively; the half-life in the terminal elimination phase average 2.6, 2.9, 4.7, or 12 hours, respectively.
Famotidine is excreted principally in urine via glomerular filtration and tubular secretion. Approximately 25 to 30% or 65 to 80% of a dose is excreted unchanged in urine within 24 hours following oral or IV administration, respectively and approximately 13 to 49% or 52 to 82% of a single 40 mg oral or IV dose, respectively, is excreted within 72 hours.