Pharmacokinetic and pharmacodynamic properties of histamine H2-receptor antagonists. Relationship between intrinsic potency and effective plasma concentrations.

摘要: Histamine H2-receptor antagonists are a unique class of compounds. Pharmacologically they characterised as family by their ability to inhibit the secretion gastric acid, and kinetically classified similarity in absorption, distribution elimination. All exhibit classical competitive drug-receptor interactions, with Schild slope parameters not significantly different from unity. Comparison values negative logarithm molar concentration antagonist presence which potency agonist is reduced 2-fold (PA2) indicates that famotidine about 20 50 times more potent than cimetidine 6 10 ranitidine. To date, most among marketed antagonists. Oral absorption all under clinical investigation fairly rapid. Peak plasma concentrations usually attained within 1 3h after dose, but second peak oral administration has been observed cimetidine, ranitidine, famotidine, ramixotidine etintidine. The mean bioavailability for H2-antagonists ranges 70%. Reports on profiles intravenous available only nizatidine: 4 decline biexponential manner. eliminated quite rapidly, terminal half-life total body clearance 24 48 L/h. Elimination mainly attributable renal excretion, clearances ranging 13.8 30 As greatly exceed glomerular filtration rate (6 7.2 L/h), it apparent tubular plays an important role. There simple, direct correlation between inhibition acid secretion. This implies rapid equilibration drug at site action, reversible interaction. Success correlating pharmacological effects stems reliable precise measurement both items. Despite heterogeneous nature data sources, 50% inhibitory (IC50) nizatidine, etintidine roxatidine obtained vitro appear be good agreement those determined vivo. These results suggest early stage development antagonist, IC50 studies may useful first approximation predict clinically effective new agent.