What are the pharmacological implications of the different activation rates of proton pump inhibitors?

John Horn PharmD: Currently, we have five proton pump inhibitors available to us here in the United States. We have omeprazole and lanzoprazole, which have been around the longest. They were followed by rabeprazole and, most recently, pantoprazole and esomeprazole.

Esomeprazole is the S-enantiomer of omeprazole. All of the proton pump inhibitors are actually in combinations of the R- and S-enantiomer. The S-enantiomer of omeprazole is very similar. In fact, it's identical to omeprazole. The reason for that is that even though we have two enantiomers of the parent compound, when the compounds convert to the sulfonamide, the active drug, those compounds are not chiral, they're planar molecules. It really doesn't matter whether you start with R-omeprazole or S-omeprazole: you end up with exactly, precisely the same active molecule. So while we have five proton pump inhibitors, in reality, we have four, because two of them are exactly the same.

The differences between these compounds lies, I think, predominantly in their pharmacology. For example, there are differences in the rapidity at which you can achieve acid suppression. Most if not all of the studies, I think, without exception, have shown that rabeprazole-perhaps because of its more rapid activation, perhaps because of its good potency compared to the other compounds-produces the most rapid suppression of acid secretion and therefore the most rapid symptom relief. I think that's a very useful feature that can be employed, particularly for patients who might be using these drugs intermittently or on demand. It's also maybe one of the reasons why rabeprazole has been the first drug, at least in this country, to receive labeling for seven-day therapy for H. pylori.

All of the proton pump inhibitors work very well in the treatment of erosive esophagitis. In fact, I think that the drugs are identical in the treatment of erosive esophagitis. It's perhaps the easiest thing to treat with these drugs. You get very, very good response rates with all of the drugs, and you have to do huge studies to show any differences whatsoever. The drugs are also used more commonly for simple GERD or heartburn, just symptomatic relief. Here's where I think we start to see some differences between the drugs: again, it is in the onset, and perhaps in the consistency, of symptom relief.

The drugs are also all used in the treatment of H. pylori. But here again, we see some differences. Most of the drugs are administered for 10 to 14 days. Rabeprazole now has been approved for seven-day therapy for H. pylori. You don't save a lot of money on the proton pump inhibitor, because all these patients are going to stay on the proton pump inhibitor for another month or two after the treatment with the antibiotics anyway, but you do save a lot of money on the clarithromycin by reducing from 14 to seven days of therapy.

John Horn PharmD