PROTON PUMP INHIBITORS

PROTON PUMP INHIBITORS

PROTON PUMP INHIBITORS: INTRODUCTION

Inhibition of the Proton Pump in the parietal cells has been established as the major therapeutic category in the treatment of acid-related diseases, such as peptic ulcer and gastro-oesophageal reflux.

Proton pump inhibitors are known to act by accumulating in the target cell and are activated by acid and bind strongly to the specific target- the proton pump.


The clinical superiority of the proton pump inhibitors is due to their high efficacy and long duration of the acid inhibition in comparison with other antisecretory drugs.Carbapenems can be grouped as (2),

Omeprazole is the very first proton pump inhibitor which was introduced in 1989; later Lansoprazole, Rabeprazole, Pantoprazole, and Esomeprazole were introduced.

Omeprazole, Lansoprazole, Rabeprazole, Pantoprazole and Esomeprazole are characterized as gastric acid pump inhibitors, in that they block the final step of acid production. Wherein Pantoprazole acts by forming a covalent bond to two sites of the (H+,K+)-ATPase enzyme system at the secretory surface of the gastric parietal cell. The inhibitory effect is dose-related and leads to inhibition of both basal and stimulated gastric acid secretion irrespective of the stimulus.

Omeprazole, Lansoprazole, Rabeprazole, Pantoprazole and Esomeprazole, all belong to the antisecretory class of drugs and are chemically substituted benzimidazoles, where in Esomeprazole is the true S- isomer of Omeprazole.(4)

CLINICAL INDICATION FOR PROTON PUMP INHIBITORS

Omeprazole:

Indication:

• Treatment of gastric ulcer (GU), erosive esophagitis (EE), and gastroesophageal reflux disease (GERD) with or without esophageal lesion.
• Maintenance therapy of EE.
• Eradication of Helicobacter pylori in triple therapy with clarithromycin and amoxicillin or in double therapy with clarithromycin only.

Lansoprazole:

Indication:

• Treatment of duodenal ulcer (DU), both H. pylori positive and negative, active benign GU, GERD, EE and pathological hypersecretory conditions, including Zollinger-Ellison syndrome (ZES).
• Maintenance therapy of DU and EE.
• Eradication of H. pylori in triple therapy with clarithromycin and amoxicillin, or in double therapy with amoxicillin only.

Rabeprazole:

Indication:

• Treatment of erosive or ulcerative GERD, DU and hypersecretory syndromes including ZES.
• Maintenance of erosive or ulcerative GERD.

Pantoprazole:

Indication:

• Treatment of EE (erosive esophagitis) associated with GERD (gastroesophageal reflux disease).

Esomeprazole:

Indication:

• In the treatment of GERD, healing of EE, maintenance of healing of EE, H. pylori Eradication to reduce the risk of duodenal ulcer recurrence in triple therapy with clarithromycin and amoxicillin.

 The following Proton Pump Inhibitors:

Omeprazole as:
Omeprazole	Capsules	20mg, 40mg	Strip, Blister	10's
Omeprazole	Lyophilised Injection	40mg	Vial	10ml Vial
Omeprazole Sodium with Sodium Bicarbonate	Tablets	20mg, 40mg	Blister	10's
Lansoprazole as:
Lansaprazole	Capsules	30mg	Strip	10's
Rabeprazole as:
Rabeprazole	Tablets	10mg, 20mg	Blister	10's, 15's
Rabeprazole Sodium with Sodium Bicarbonate	Tablets	10mg, 20mg	Blister	10's, 15's
Pantoprazole as:
Pantoprazole	Tablets	20mg, 40mg	Blister	10's
Pantoprazole	Lyophilised Injection	40mg	Vial	1's

Pharmacokinetic parameters of PPIs
Parameter	Esomeprazole	Lansoprazole	Omeprazole	Pantoprazole	Rabeprazole
Bioavailability	90%	80%-85%	30%-40%	77%	52%
Enteric-coated formulation	Capsule	Capsule	Capsule	Tablet	Tablet
Time to peak plasma concentration	1.5 hours	1.7 hours	0.5-3.5 hours	2.5 hours	2-5 hours
Half-life (plasma)	1.2-1.5 hours	1.5 hours	0.5-1 hour	1 hour	1-2 hours
Major cytochrome P450 pathway	CYP2C19	CYP3A, CYP2C19	CYP2C19	CYP2C19	CYP3A CYP2C19
Protein binding	97%	97%	95%	98%	96.3%