Most of us have seen patients who just do not make sense. How can a 300 lb woman need 15 mg of morphine while the 100 lb man requires 200 mg? The answer is usually multifactorial and includes pharmacogenetics, pharmacokinetics, and pharmacodynamics. However, opioid malabsorption may also be in that mix explaining why some opiates work for some but not others.
Most oral opiates are absorbed in the small intestine and travel to the liver where they are metabolized. Opiates are mostly metabolized via the cytochrome P450 enzymes and glucuronidation. Some opiates begin metabolism via CYP450 enzymes before the opioid crosses the intestinal wall. We know genetic polymorphisms exist in the CYP450 pathways which can explain some variability in opioid response. Next to the liver, the small intestine has the second highest concentration of CYP450 enzymes. So it is reasonable to posit that without adequate CYP450 function, opioids may not metabolize in the small intestine and subsequently fail to absorb into the bloodstream. The role of opiate receptors in the small intestine is not well understood. Perhaps the receptor enzyme complex plays a significant role in signal processing and transport resulting in a malabsorption syndrome explaining why there are such variances in opioid response and tolerance.
Opioid Malabsorption Syndrome should be considered any time a patient reports failure of multiple oral opiates. These patients may be a candidate for opioid tolerance testing.