What If You Could Take Bisphosphonates Without the Side Effects?
Due to poor compliance issues with bisphosphonates, companies are working on new delivery systems that would cut down or eliminate the gastrointestinal and esophagus problems seen with these drugs.
For years, bisphosphonates have been the gold standard for osteoporosis treatment, but these medications come with a lot of restrictions and problems with gastrointestinal and esophagus issues that some people just can't handle due to the damage they can cause.
These medications have a poor permeability while in the stomach making it difficult for our bodies to absorb the full amount of the active ingredient that is necessary to slow bone resorption. Because these medications have to be taken on an empty stomach with water only, plus you have to wait to eat and stay upright for 30-60 minutes - depending on which dosage you are taking - approximately 60% of patients stop taking the treatment within a year, so their bone mineral density doesn't have a chance to improve.
Complex dosing regimes, postural restrictions and GI side effects were the main reasons patients discontinued treatment according to the International Osteoporosis Foundation.
Merrion Pharmaceuticals is in the process of approving a new delivery system using
Gastrointestinal Permeation Enhancement Technology (GIPET) TM enhancers-and enteric coating-causing a timed released form of alendronate to be absorbed while in the small intestine.
The company did studies with their delivery system in combination with alendronate, marketed by Merck as Fosamax®, and found that much less active ingredient had to be used since the product promotes greater absorbability, which translates into fewer side effects in the gastrointestinal tract. Esophageal problems are greatly reduced because you don't have the reflux, of the stomachs contents, which damages the esophagus.
The fasting bioavailability of Fosamax® is .06% which decreases even more when taken with food. Merrion Pharmaceuticals MER 103 technology enhances the bioavailability of alendronate in the small intestine by adding a proprietary blend of ingredients that have GRAS status, to their enteric coated formula.
Merrion Pharmaceuticals uses food additives with the GRAS (generally recognized as safe) identification; generally, these are food additives that have normal dietary components with long records of safe use.
In studies conducted by Merrion, "An oral dose of Fosamax® was the reference drug, taken as per label. Based on urinary excretion data for alendronate, MER 103 (almerol) gave an increase in relative bioavailability of approximately 15 fold when dosed at night time, 12 fold when dosed fasted overnight and 3 fold when dosed with a high fat breakfast (Merrion Pharmaceuticals 2007)." With the increased bioavailability seen with this technology, patients can take smaller amounts of a bisphosphonate at potentially reduced frequency, with greatly reduced side effects.
Looking at the results, there were several benefits to this study. Participants were able to take the dose at night rather than in the morning without food. Postural restrictions-staying upright for a designated time-were eliminated and a smaller amount of the drug was equivalent to the weekly Fosamax® dose, so they were able to take less of the active ingredient, reducing side effects.
We see that even in this study, the treatment results were better when taken in a fasting state; however eating food with this did not drastically decrease the absorption, like it would have with just Fosamax®. Because MER 103 absorbs in the small intestines, there were no gastro intestinal, or other serious adverse issues reported by the group. The company presented this clinical data to The North American Menopause Societies annual meeting in October 2007.
Merrion Pharmaceuticals MER 103 (almerol) technology received the 2008 Frost and Sullivan Osteoporosis Technology Innovation of The Year Award.
This technology is not available to us yet, but hopefully it will be in the near future with the positive clinical data presented so far, and since Merck's patent has expired leaving a gap that a new application could fill using the generic form of Fosamax® (alendronate) that has excellent prospects.