Metabolism of OPs is mediated by the paraoxonase1 enzyme (PON1), whereby fast metabolizers suffer less AChE inhibition than slow metabolizers in response to the same level of exposure (Costa et al. 2005).
Some patients are fast metabolizers of oxycodone, resulting in reduced analgesic effect but increased adverse effects, while others are slow metabolizers resulting in increased toxicity without improved analgesia (Gasche et al. 2004).
Citalopram, the most commonly used antidepressant at BPH, is primarily metabolized by both the cytochrome enzymes, and patients who have gain-of-function mutations in these genes are fast metabolizers and exhibit a poor response to citalopram.
For example, "slow metabolizers" of tamoxifen may have a worse outcome in the adjuvant setting with tamoxifen treatment than "fast metabolizers," suggesting that these patients might be better treated with an AI [ 33– 33].
A recent Pharmacogenetics study conducted in Tanzanian adults indicated the frequencies of CYP2B6 genotypes to be 37%, 45%and16%6% for homozygous wild type (fast metabolizers), heterozygous (intermediate) and homozygous mutated (poor metabolizers) repectively [ 22].
Using 1,2-C-DCA, several researchers were able to clearly segregate "slow" and "fast" metabolizers of DCA, based on GSTz1/MAAI (Shroads AL, Langaee T, Coats BS, Kurtz TL, Bullock JR, Weithorn D, Gong Y, Wagner DA, Ostrov DA, Johnson JA, Stacpoole PW, unpublished observations).
Rats have been reported to be much faster metabolizers of arsenic than humans [ 51], but based on this study this is attributed to other factors.
