Absorption, distribution, metabolism and excretion pharmacogenomics of drugs of abuse

Abstract

Pharmacologic and toxic effects of xenobiotics, such as drugs of abuse, depend on the genotype and phenotype of an individual, and conversely on the isoenzymes involved in their metabolism and transport. The current knowledge of such isoenzymes of frequently abused therapeutics such as opioids (oxycodone, hydrocodone, methadone, fentanyl, buprenorphine, tramadol, heroin, morphine and codeine), anesthetics (γ-hydroxybutyric acid, propofol, ketamine and phencyclidine) and cognitive enhancers (methylphenidate and modafinil), and some important plant-derived hallucinogens (lysergide, salvinorin A, psilocybin and psilocin), as well as of nicotine in humans are summarized in this article. The isoenzymes (e.g., cytochrome P450, glucuronyltransferases, esterases and reductases) involved in the metabolism of drugs and some pharmacokinetic data are discussed. The relevance of such data is discussed for predicting possible interactions with other xenobiotics, understanding pharmacokinetic behavior and pharmacogenomic variations, assessing toxic risks, developing suitable toxicological analysis procedures, and finally for interpretating drug testing results.