Pantomide Mechanism of Action

Pharmacotherapeutic group: Pantoprazole: Proton pump inhibitors. Domperidone: Domperidone is a peripheral dopamine (D2) and (D3) receptor antagonist. ATC code: Pantoprazole: A02BC02. Domperidone: A03FA03.
Pharmacology: Mechanism of Action: Pantoprazole, a benzimidazole sulphoxide derived prodrug, is an irreversible proton pump inhibitor. Pantoprazole, being a weak base, is highly ionized at low pH and readily accumulated in the highly acidic canalicular lumen of the stimulated parietal cell in the stomach. In this acidic environment, it is protonated and rapidly converted to a cationic cyclic sulphonamide. The sulphonamide binds covalently to cysteine residues on the luminal (acidic) surface of H+/ K+-ATPase to form a mixed disulphide; thus causing irreversible inhibition of the gastric proton pump. This inhibition of the gastric proton pump or H+ / K+ -ATPase (which represents the final step in the secretory process), suppresses gastric acid secretion.
Domperidone, a benzimidazole derivative (structurally related to the butyrophenones), acts by selectively antagonizing the peripheral dopaminergic, receptors in the gastrointestinal (G.I.) wall, thereby enhancing gastrointestinal peristalsis and motility and increasing Lower Esophageal Sphincter (LES) tone.
Pharmacokinetics: Pantoprazole: Pantoprazole is rapidly absorbed after oral administration, with peak plasma concentrations (C_max) of 1.1 to 3.1. (mean 2.1) mg/L max occurring within 2 to 4 (mean 2.7) hours (t_max) after ingestion of an enteric max coated 40 mg tablet. The volume of distribution is low (mean 0.16 L/kg at steady state) due to high degree of plasma protein binding (-98%). Plasma Pantoprazole concentrations decline monophasically after oral administration, with a mean plasma terminal half-life (ty,P) of 0.9 to 1.9 hours. However, since inhibition of acid secretion is non-competitive or irreversible, there is no correlation between plasma levels and the duration of action of Pantoprazole. Concomitant intake of food has no influence on the bioavailability of Pantoprazole, and any possible retardant effect of food on the rate of drug absorption is not of clinical relevance, considering the prolonged antisecretory action of Pantoprazole. The enteric coating does not influence the bioavailability of Pantoprazole. Pantoprazole undergoes extensive hepatic metabolism via cytochrome P450 oxidase followed by sulphate conjugation. Elimination of Pantoprazole is predominantly renal, with -80% of an oral dose being excreted as urinary metabolite; the remainder is excreted in the feces and originates primary from biliary secretion.
Domperidone: Domperidone is rapidly and almost completely (93%) absorbed after oral administration. Peak plasma concentrations occur within 30 min. after oral administration. The peak plasma concentration value after a 20 mg oral dose is in the range of 15 to 19 ng/ml. The mean elimination half-life ranges from 12-16 hours for an oral dose. Oral bioavailability of Domperidone is 13-17% because of extensive pre systemic metabolism in gut wall and liver. Administration of Domperidone 90 minutes after a meal increases bioavailability whereas Cimetidine or alkali pretreatment reduces bioavailability. Domperidone is strongly bound to plasma proteins (90- 93%). Domperidone undergoes extensive biotransformation with <1% excreted unchanged in urine.