Axid is a competitive, reversible inhibitor of histamine at the histamine H₂-receptors, particularly those in the gastric parietal cells.

Antisecretory Activity — 1. Effects on Acid Secretion: Axid significantly inhibited nocturnal gastric acid secretion for up to 12 hours. Axid also significantly inhibited gastric acid secretion stimulated by food, caffeine, betazole, and pentagastrin (Table 1).

2. Effects on Other Gastrointestinal Secretions — Pepsin: Oral administration of 75 to 300 mg of Axid did not affect pepsin activity in gastric secretions. Total pepsin output was reduced in proportion to the reduced volume of gastric secretions.

Intrinsic Factor: Oral administration of 75 to 300 mg of Axid increased betazole-stimulated secretion of intrinsic factor.

Serum Gastrin: Axid had no effect on basal serum gastrin. No rebound of gastrin secretion was observed when food was ingested 12 hours after administration of Axid.

3. Other Pharmacologic Actions —

a. Hormones: Axid was not shown to affect the serum concentrations of gonadotropins, prolactin, growth hormone, antidiuretic hormone, cortisol, triiodothyronine, thyroxin, testosterone, 5a-dihydrotestosterone, androstenedione, or estradiol.

b. Axid had no demonstrable antiandrogenic action.

4. Pharmacokinetics — The absolute oral bioavailability of nizati-dine exceeds 70%. Peak plasma concentrations (700 to 1,800 ^mg/L for a 150-mg dose and 1,400 to 3,600 ^mg/L for a 300-mg dose) occur from 0.5 to 3 hours following the dose. A concentration of 1,000 ^mg/L is equivalent to 3 ^mmol/L; a dose of 300 mg is equivalent to 905 ^mmoles. Plasma concentrations 12 hours after administration are less than 10 ^mg/L. The elimination half-life is 1 to 2 hours, plasma clearance is 40 to 60 L/h, and the volume of distribution is 0.8 to 1.5 L/kg. Because of the short half-life and rapid clearance of nizatidine, accumulation of the drug would not be expected in individuals with normal renal function who take either 300 mg once daily at bedtime or 150 mg twice daily. Axid exhibits dose proportionality over the recommended dose range.

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