Pass the tablet please - Editorial - intestinal absorption in the elderly

Alternative Medicine Review, August, 2003 by Al Czap

What do some 69.3 and 73.8 year-olds have in common?

a. Because of their ages they quite likely have compromised digestive ability and subsequent inhibited absorption capability.

b. They have participated in a study relating to memory or cognitive function.

c. Both of the above.

If you answered "c" you are correct; however, the results of these studies are in question due to both answer (a) above and study design.

In "Ginkgo for Memory Enhancement," JAMA 2002; 288(7):835-840, Solomon states that published Ginkgo studies regarding memory and cognitive function are not supported by "well-controlled clinical studies," of which there are many. He then designs a study of patients with a mean age of 69.3, utilizing Ginkgo tablets and lactose capsules as a placebo--not really a double-blind control.

In "Effects of Rofecoxib or Naproxen vs. Placebo on Alzheimer Disease Progression," JAMA 2003; 289(21):2819-2826, Aisen enlisted patients with a mean age of 73.8 and used as part of the study "over-encapsulated" rofecoxib tablets (in which a tablet is placed inside of a capsule) so the placebo (capsules) would appear the same. His aim was to see if anti-inflammatory drugs have a protective effect, reducing the incidence of Alzheimer's disease.

In addition to using different dosage forms for their drug and placebo, neither study actually measures absorption of the active ingredient by the study participants, a critical point when studying an elderly population, who have a higher incidence of hypo- and achlorhydria. Also, both studies used a dosage form that contains a dissolution-inhibiting excipient, magnesium stearate. Neither study measured even a portion of the participant's digestive ability, either by Heidelberg pH or comprehensive stool analysis. Going back more than two decades the Journal of the American Geriatric Society, 1980 Jan 28(1):42-45, Baker et al found many elderly unable to absorb vitamins from tablets.

In Aisen's study, one would hope to gain insight into the dynamics by reviewing the area under the plasma concentration versus time curve (AUC) or the peak plasma drug concentration (Cmax) in the elderly by referencing the PDR. In the PDR, the rofecoxib tablet mechanism of action describes a 34-percent increase in AUC in patients over 65 compared to young patients, but does not state the time frame or level of Cmax, which could be interpreted as the excipients creating a time-release atmosphere in the elderly. A 20-percent decrease in Cmax is also noted in the elderly after administration of antacids that influence digestion, but no further data is given.

It has long been my opinion that unless a drug is provided in a dosage form without any dissolution-inhibiting excipients such as magnesium stearate, comprehensive studies on the elderly or those with compromised digestive systems must be performed before market approval is given. Studies such as those cited above should also have taken these factors into consideration.

Just hang out with the septic tank pump service truck one day. When he pumps Aunt Ingrid's tank, you might just find a layer of tablets in the bottom--anti-depressants, no doubt!