Esoferr Mechanism of Action

Pharmacology: Pharmacodynamics: Esomeprazole, a proton pump inhibitor, is the S-isomer of omeprazole. Esomeprazole is a weak base and is concentrated and converted to the active form in the highly acidic environment of the secretory canaliculi of the parietal cell, where it inhibits the enzyme H⁺/K⁺-ATPase- the acid pump and inhibits both basal and stimulated acid secretion. Esomeprazole blocks the final step in acid production, resulting in potent, long-lasting inhibition of gastric acid secretion.
Pharmacokinetics: DR cap: The area under the plasma concentration-time curve from time zero to the last observed quantifiable concentration (AUC_0-t), area under the plasma concentration-time curve from time zero to infinity (AUC_0-inf), the peak plasma concentration of the drug (C_max), time needed to achieve the peak plasma concentration (t_max) and the elimination hal-life (t_1/2) of esomeprazole were defined as the main parameters in the bioequivalence study of ESOFERR 40 mg.
The arithmetic means AUC_0-t, AUC_0-inf, C_max and t_1/2 for the test drug T₁ were 4497.55 (2624.01) ng·hour/ml, 4815.51 (2612.49) ng·hour/ml, 1929.08 (801.82) ng/ml, and 1.29 (0.47) hours, respectively, with the median (range) t_max of 2.00 (1.00-4.00) hours. The arithmetic means AUC_0-t, AUC_0-inf, C_max and t_1/2 for the test drug T₂ were 4635.49 (2952.30) ng·hour/ml, 4976.08 (2961.25) ng·hour/ml, 1789.35 (792.10) ng/ml, and 1.25 (0.47) hours, respectively, with the median (range) t_max of 2.25 (1.25-5.00) hours. The arithmetic means AUC_0-t, AUC_0-inf, C_max and t_1/2 for the comparator product R₁ were 4376.89 (2645.21) ng·hour/ml, 4698.43 (2625.27) ng·hour/ml, 1824.12 (763.69) ng/ml, and 1.29 (0.44) hours, respectively, with the median (range) t_max of 2.13 (0.75-5.00) hours. The arithmetic means AUC_0-t, AUC_0-inf, C_max and t_1/2 for the comparator product R₂ were 4329.59 (2765.75) ng·hour/ml, 4626.35 (2827.19) ng·hour/ml, 1808.73 (784.53) ng/ml, and 1.20 (0.52) hours, respectively, with the median (range) t_max of 2.25 (1.25-6.00) hour.
The geometric mean ratios (90% confidence intervals) of the test drug/comparator product for esomeprazole were 102.99% (94.13-112.68%) for AUC_0-t and 101.32% (91.91-111.70%) for C_max. The t_max and t_1/2 values of test drug and comparator product for esomeprazole were found not significantly different.
The bioequivalence of the two products was concluded based on the 90% confidence interval of the test/comparator-geometric means ratio within the range of 80.00 to 125.00% for both AUC_0-t and C_max.
Hence, it was concluded that ESOFERR 40 mg was bioequivalent to the comparator drug.
Powd for inj: Distribution: The apparent volume of distribution at steady state in healthy subject is approximately 16 L. Esomeprazole is 97% plasma protein bound.
Metabolism and excretion: Esomeprazole is completely metabolized by the cytochrome P450 (CYP) isoenzyme CYP2C19 and the remainder is metabolized by the cytochrome P450 (CYP) isoenzyme CYP3A4. The major metabolites of esomeprazole have no effect on gastric acid secretion. The plasma elimination half-life is about 1.3 hours.
Esomeprazole is completely eliminated from plasma between doses with no tendency for accumulation during once daily administration.