Proton pump inhibitors include-

Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole, Pramiprazole

Refer - Omeprazole 

Proton pump inhibitors causes a profound and long lasting inhibition of gastric acid secretion. Therefore esomeprazole, lanzoprazole , omeprazole ,pantoprazole and rabeprazole, may interfere with the absoption of drugs where gastric pH is an important detreminant of bioavailability ( eg.ketoconazole, ampicillin, iron salts, digoxin, cyanocobalamin )

CYP450 system - There have been reports of interaction between omeprazole and certain drugs metabolized via the CYP450 system ( eg. cyclosporine, disulfram, benzodiazepines ).

Esmoprazole , lansoprazole, pantoprazole, and rabeprazole are extensively metabolised by CYP2C19 and CYP34A . in clinical studies antacids were used conomittantly with these agents

Rabeprazole may interact with other medication by increasing gastric pH and altering their absorption.

Elimination half-life of digoxin increases upon the administration rabeprazole Studies have indicated that drug interaction with other drugs metabilised by cytochrome P-450 enzyme system

U.S. FDA APPROVED DRUGS FROM 01-01-08 TO 31-12-08

Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole, Pramiprazole

Refer - Omeprazole 

Duodenal and gastric ulcer. Reflux osesophagitis

Rabeprazole is well tolerated in both long-term and short-term clinical trials.

Headaches, diarrhea, rash, infection and flu syndrome are the observed adverse effects

None reported

Special precautions:

Rabeprazole should be used with caution in patients with severe hepatic impairment

Approved on   August  1991

Indications:

Duodenal and gastric ulcer.

Dosage:

Duodenal ulcer- 20mg/day for 4 weeks Zollinger- Elilison syndrome- 60mg/day

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible

 2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

GASTRO OSEPHAGEAL REFLUX DISEASE (GORD)

Evidence Based Medicine (MIMS- March 2003)

Beneficial

1. Proton Pump Inhibitors such as omeprazole, Lansoprazole, pantoprazole

2. H-2 Antagonists such as cimetidine, ranitidine, famotidine, (less than proton pump inhibitors)

3. Fundoplication

Likely to be beneficial

1. Medical and surgical tretment of GORD in selected patients with extraoesophageal manifestations.

Unknown effectiveness

1. Medical and surgical treatment of GORD in patients with Barrets oesophagus

2. Surgical treatment for non erosive oesophagitis

Key Points

1. One systemic review of randomised clinical trials has found proton inhibitors to be more effective than H-2 antagonists in both erosive and non-erosive oesophagitis. One trial has found no significant differences in the effectiveness of different proton pump inhibitors

2. Surgical treatment has not been adequately evaluated in controlled clinical trials. Medical and surgical treatments have not been adequately compared

3. It is not clear whether patients with Barretts oesophagitis benefit from medical or surgical treatment of their gastro oesophageal reflux

4. There is limited, conflicting evidence on the basis on the benefits of treating gastro oesophageal reflux in patients with extra oesophageal manifestations (such as asthma)

Refer - Omeprazole

Pharmacology:

Rabeprazole is effective in treatment, for the healing and relief of symptoms of duodenal and benign gastric ulcers of GERD and for the maintenance of healed ulcers. H-pylori eradication. It causes dose dependent inhibition of acid secretion and has a more rapid onset of action. Rabeprazole causes dose dependent inhibition of histamine-stimulated acid secretion.

Pharmacokinetics:

Rabeprazole is rapidly absorbed after oral administration. The oral bioavailability of rabeprazole is approximately 52%. The time to reach cmax is about 2.9 to 3.8 hrs. after administration of a single dose of 10 -80mg.

The drug is 96.3% plasma bound. it is rapidly cleared from the body by hepatic metabolism and renal excretion.The drug has a half-life of 1 hour after administration of single or multiple doses of 10-80mg. After administration of radiolabeled rabiprazole,approximately 90% of the dose was excreted in the urine and the remaining was excreted in the faces.The plasma elimination half-life of rabeprazole is 1-2 hrs.