My apologies to those regular readers who may have noticed my recent case of blogger’s malaise. A combination of family sicknesses and having to write a fair bit for the day job seems to have interfered with this week’s blogging.
So, what to do? Link to other worthy blogs!
This gives me an opportunity to introduce our fairly-recent addition to the ScienceBlogs corral, Karen Ventii and ScienceToLife. Karen is a late-stage biochemistry Ph.D. student down the road apiece at Emory University and posted earlier this morning on the FDA decision to reclassify the prescription diet pill, Xenical (orlistat), for over-the-counter use in the US.
Orlistat works by inhibiting an enzyme called lipase that is produced by the pancreas and secreted into the small intestine. The purpose of pancreatic lipase is normally to hydrolyze or break apart dietary triglycerides into their free fatty acids. Free fatty acids can then either be oxidized for energy, if you need it due to exercise, or stored in fat tissue.
By inhibiting lipase, orlistat causes triglycerides to pass freely through the intestines and out into the municipal water treatment stream. According to Xenical prescribing information (PDF here), “as undigested triglycerides are not reabsorbed, the resulting caloric deficit may have a positive effect on weight control.”
Hence, loose, fatty stools are a common side effect of orlistat. (The ever-eloquent Kevin Beck holds forth on this aspect of orlistat at Dr Bushwell’s Chimpanzee Refuge). However, this side effect can be reduced by – you guessed it – a low-fat diet.
This case reminds me that one of the basic concepts I’ll need to address are the criteria used by FDA to determine whether a drug is suited for reclassification from prescription-only to over-the-counter status. What concerns me about widespread use of orlistat are the potential side effects noted by Karen:
1. Orlistat may prevent the absorption of some dietary vitamins which need fat be absorbed by the body (vitamins A, D, E and beta-carotene).
2. Orlistat may increase the risk of oxalate-related kidney stones.
3. It may induce oily stools, oily spotting on underwear and urgent bowel movements.
Malabsorption of fatty vitamins can be remedied by supplementation, but this raises some questions for me about how orlistat might influence the absorption of other drugs one might be taking. The list of drugs tested for interaction noted by the manufacturer seems rather short to me. The only interaction noted was with cyclosporine, a drug taken to prevent organ transplant rejection. Orlistat reduces blood levels of cyclosporine so it should be taken two hours apart from the transplant rejection drug – or, optimally, not at all since most transplant patients are required anyway to be on regular exercise regimens as a condition of their continued rehabilitation.
Moreover, kidney stones are no laughing matter and people at risk of such stones very carefully manage their diets. I hope that the OTC labeling for orlistat includes a prominent warning for these patients because this interaction is not entirely obvious.
Note added in proof: Adding to the lighter-hearted side of this story, Pharmagossip has a clever play on the proposed brand name of this drug, Alli, and the not-so-lighthearted potential for its potential to interfere with the efficacy of oral contraceptives.