Bioavailability, Patient Preference & Placebo Effect Vis á Vis Various Forms of Chinese Ready-made Medicines

by Bob Flaws , L.Ac., FNAAOM (USA), FRCHM (UK)

Keywords: Chinese medicine, Chinese herbal medicine, bioavailability, patient preference, placebo effect

When treating patients with internally administered Chinese medicinals, most practitioners place primary importance on the correct selection of a formula in terms of the patient's disease diagnosis and Chinese medical pattern discrimination, and, of course, that is where the emphasis should be. However, almost as important are the issues of bioavailability, patient preference, and placebo effect, all of which significantly affect therapeutic outcomes. Ready-made Chinese medicines for oral administration mainly come in two forms: 1) pressed tablets (and caplets) and powder-filled capsules, and there are real differences in bioavailability, patient preference, and placebo effect between these two methods of administration. In my opinion, professional practitioners of Chinese medicine should take these differences into account when deciding which ready-made Chinese medicines to prescribe and dispense. Such a decision may very well make the difference between clinical success and failure.

Bioavailability

In pharmacology, bioavailability describes the fraction of an administered dose of medication that reaches the systemic circulation, and it is one of the principal pharmacokinetic properties of any and all medicinals, including Chinese "herbs." By definition, when a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via other routes (such as by mouth), its bioavailability decreases (due to incomplete absorption and first-pass metabolism). Bioavailability is one of the essential tools in pharmacokinetics and should be considered when calculating dosages for non-intravenous routes of administration,1 and per os or oral administration is such a non-intravenous route. Various physiological factors reduce the extravascular availability of medicinals prior to their entry into the systemic circulation. Such factors may include, but are not limited to:

1. Poor absorption from the gastrointestinal tract
2. Degradation or metabolism of the medicinal prior to absorption
3. Hepatic first-pass effect

Each of these factors may vary from patient to patient and, indeed, in the same patient over time. For instance, whether a drug is taken with or without food will affect absorption. Other drugs taken concurrently may also alter absorption and first-pass metabolism, while intestinal motility alters the dissolution of the drug and may affect the degree of chemical degradation of the drug by intestinal microflora. Further, disease states affecting liver metabolism or gastrointestinal function will also have an effect.2

However, the bioavailability of medicinals which are swallowed and absorbed through the gastrointestinal tract is also markedly affected by the form of medication. According to Laurel Kallenbach in the August 1999 edition of Vegetarian Times, "In some cases, as little as 15 percent to 20 percent of a supplement will be delivered to your cells."3 In such cases, the other, nonabsorbed nutrients or medications simply go to make up very expensive urine. Tablets (including caplets) are formed by applying tons of direct pressure to a powder at high temperatures. Besides pressing the ingredients together into a hard mass, this can cause a decomposition of active ingredients. In addition, many "inactive" ingredients, primarily sugars, starches, and bonding agents (glue), are added to the formulas in order to hold all the substances in a tablet. Some tablets also have chemical coatings that are added to make them easier to swallow and mask the taste of powders. The end result of all this is that tablets (and caplets) will often pass through the entire digestive system undissolved or only partially dissolved without absorption. In a capsule form, free-flowing powdered ingredients become available for absorption in a matter of a few minutes after swallowing. Research (as well as common sense) suggests that oral administration of medicinals in gelatin capsules results in better bioavailability of those medicinals than when administered in the form of pressed tablets. For instance, a study published in British Journal of Dermatology (1985, Vol. 112, p. 469) showed that bioavailability of the drug 5-methoxypsoralen (a constituent of many Chinese herbs) was significantly greater (P < 0.01) after administration in capsule form over tablets.4 Similarly, according to research carried out by the Sichuan Pudu Pharmaceutical Company, glimepiride capsules (a hypoglycemic drug) possess better bioavailability and patient compliance compared to glimeride tablets.5 For more than 20 years, Jack Challem has served as a nutrition reporter for numerous consumer health magazines, including Let's Live, Natural Health, Prime Health & Fitness, and Health Naturally (Canada). According to Challem in an article titled, "Why you don't absorb the nutrients you should—and what you can do about it," tablets take much longer to break down and, instead, wind up passing through one's system either partially or wholly unused. Based on this, it is Challem's advice that "Whenever possible..., opt for capsules" when buying nutritional and herbal supplements.6

Patient preference

Like bioavailability, patient preference in terms of dosage forms may also affect therapeutic outcomes. If a patient does not like the form of administration of a particular medicine, they are less likely to take that medicine as prescribed by their health care provider. In other words, preference directly affects compliance or adherence. Obviously, if patients do not take their medicine as prescribed, they are also not likely to get the intended therapeutic effect, and, when it comes to capsules versus pills, a number of studies have shown that capsules are what patients prefer. For instance, according to a study carried out in 1982 by the Burke Marketing Research Institute on the patient acceptance of solid oral dosage forms, 96% of the 1,000 patients queried had very definite ideas on what is most acceptable to swallow. In this study, the majority of patients, i.e., 54%, expressed preference for a drug in capsule dosage form. Only 29% of those asked opted for coated tablets, while only 13% favored standard (uncoated) tablets. In another study conducted in 1990 which involved 7,000 patients in five European countries, gelatin capsules were the most strongly associated form of oral medication with perceptions of "effectiveness" and "easiness to swallow."7 In 1997, Povlin Research queried 700 nutritional supplement users about their preference in solid oral dosage forms. Four hundred of these were herbal users and 300 were vitamin users. According to this study, the majority of herbal users, 74%, expressed preference for two-piece capsules, while vitamin users preferred the two-piece capsule over a tablet by a 2-to-1 margin. In this case, ease-of swallowing was the dominant reason (66%) for preferring capsules over tablets.8

Placebo effect

The placebo effect (Latin placebo, "I shall please") was first mentioned in 1955 by Henry K. Beecher, M.D. It is also known as non-specific effects and the subject-expectancy effect.9 It is the phenomenon that a patient's symptoms can be alleviated by an otherwise ineffective treatment since the individual (and/or their care-giver) expects or believes that it will work. A person's beliefs and hopes about a treatment, combined with their suggestibility, may have a significant biochemical effect. Sensory experience and thoughts can affect neurochemistry. The body's neurochemical system affects and is affected by other biochemical systems, including the hormonal and immune systems. Thus, it is consistent with current knowledge that a person's hopeful attitude and beliefs may be very important to their physical well-being and recovery from injury or illness.10 In an article titled, "The Healing Power of Placebos," Tamar Nordenberg states that, "For a given medical condition, it's not unusual for one-third of patients to feel better in response to treatment with placebo."11 According to research carried out at the UCLA Neuropsychiatric Institute, between 30-60% of patients with illnesses ranging from arthritis to depression report a substantial improvement in their symptoms after receiving a placebo.12 Further, "There is a placebo factor in every therapeutic maneuver"13 or act. In terms of what this means in clinical practice, an independent study carried out by Dr. M. Z. Hussain published in British Journal of Psychiatry (1972, Vol. 120, p. 507-509) found that capsules, in comparison to other oral dosage forms, are consumed more regularly and that more patients requested continuation of treatment with capsules, indicating their belief of the positive impact of the capsule dosage form. Because this study found that the actual physical form of the medication could act as an important additive ancillary factor in the placebo response, most clinical trials of psychiatric-directed medicines are required to use the capsule dosage form.14

Conclusion

Based on the foregoing, I highly recommend professional practitioners to consider that different dosage forms of orally administered Chinese ready-made medicine may well achieve different therapeutic outcomes regardless of their other differences, such as ingredients and their proportions or their extract ratios or potencies. As practitioners, we need to remember that the healing encounter is a multifactorial transactional experience and that far more is involved beyond simply getting the formula or its ingredients right for any given patient. If we keep in mind and, more importantly, act on such factors as bioavailability, patient preference, and placebo effect, we will bring more of these factors to bear in that encounter with the intention of achieving better outcomes for all involved.

Copyright © Blue Poppy Press, 2006. All rights reserved.

Endnotes:
1. http://en.wikipedia.org/wiki/Bioavailability
2. Ibid.
3. http://findarticles.com/p/articles/mi_m0820/is_1999_August/ai_55266467
4. http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2133.1985.tb02322.x#search=%22capsules%20%2B%20bioavailability%22
5. http://www.pudu.com/doce/cpjs.shtml
6. Ibid.
7. http://findarticles.com/p/articles/mi_m0820/is_1999_August/ai_55266467
8. http://answers.google.com/answers/threadview?id=536724
9. http://en.wikipedia.org/wiki/Placebo_effect
10. http://skepdic.com/placebo.html
11. http://www.fda.gov/fdac/features/2000/100_heal.html
12. http://www.placebo.ucla.edu/
13. http://home.comcast.net/~bkrentzman/meds/placebo.html
14. http://www.capsugel.com/services/rx_dpstdy.php