Magazine article Drug Topics

Newest Proton Pump Inhibitor Approved for Gastrointestinal Ills

Magazine article Drug Topics

Newest Proton Pump Inhibitor Approved for Gastrointestinal Ills

Article excerpt

Two's company and three's no crowd. The recently approved proton pump inhibitor (PPI) Aciphex (rabeprazole sodium) joins the other two big guns of the acidsuppression army in the front lines against gastrointestinal woes.

Comarketed by Eisai Inc. and Janssen Pharmaceutica, rabeprazole is indicated for healing of erosive gastroesophageal reflux disease (GERD); maintenance of healed erosive GERD; healing of duodenal ulcers; and treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

Similar to the other PPIs (omeprazole and lansoprazole), this new agent is thought to suppress gastric acid secretion by inhibiting gastric H+, K- ATPase at the secretory surface of the gastric parietal cell. And, like its pharmacologic relatives, rabeprazole has demonstrated impressive healing effects in GERD.

Results from a multicenter wellcontrolled study indicate that the antisecretory drug-at 10, 20, and 40 mg q.d.-was significantly superior to placebo in producing endoscopic healing after four and eight weeks of treatment in patients with erosive or ulcerative GERD. A comparative study found rabeprazole (20 mg q.d.) to be more effective than an He antagonist in the treatment of the same con dition.

In differentiating the new drug from the other PPIs, David Earnest, M.D., professor of medicine and gastroenterology at the University of Arizona, College of Medicine, highlighted several of its features. One rather favorable, pharmacokinetic characteristic rabeprazole possesses is the ability to inhibit the proton pump at a wider range of gastric acidity, Earnest pointed out. "One of the problems with the other PPIs is that they tend to require the presence of a lot of acid for optimal effects," he claimed. Currently, administration of both omeprazole and lansoprazole is recommended before meals--a time when gastric acidity tends to be higher. Rabeprazole's labeling does not specify drug administration in relation to meals, but it does state that the effect of food on drug absorption has not been evaluated.

Rabeprazole's other beneficial characteristic may be a potentially rapid onset of action. Earnest referred to in vitro studies indicating that the agent inactivates almost 100% of the proton pumps within five to 10 minutes of contact.

Although rabeprazole is metabolized by the cytochrome P450 enzyme system, it has not been shown to interact with cytochrome P450-dependent drugs, including warfarin, theophylline, diazepam, and phenytoin. The antisecretory agent, however, did inhibit metabolism of cyclosporin during in vitro studies. Like other PPIs, rabeprazole may interact with compounds that are dependent on gastric pH for absorption. For example, coadministration of rabeprazole and ketoconazole resulted in a decreased bioavailability of ketoconazole, while the combined use of rabeprazole and digoxin resulted in an increased AUC and C^sub max^ for digoxin.

Of the adverse effects reported during clinical trials, headache was the most common occurrence. It should be noted that more serious adverse effects have been observed in worldwide post-marketing experience; some of these effects were sudden death, coma, hyperammonemia, TSH elevations, and interstitial pneumonia. In most instances, the relationship of these events with rabeprazole was unclear.

The use of PPIs in the management of GERD-a condition characterized by a retrograde flow of gastric contents to the esophagus due to a transient relaxation of the lower esophageal sphincter-has become more widespread over the past few years. …

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