The pharmacokinetics of drugs are typically encompassed by four categories: absorption, distribution, metabolism and elimination.
Absorption
Absorption of opioids depends on the route of administration. Orally administered opioids are ingested, then travel through the gastrointestinal tract to be absorbed by mucosa in the stomach and intestines. High ionization in the stomach reduces absorption of opioids and subsequently reduces bio-availability of opioids to 50%. Additionally, orally administered opioids undergo first-pass effect in the liver, since they travel from the gastrointestinal tract to the liver, where they are metabolized, before being distributed into systemic circulation. Opioids which are administered intravenously (IV) are absorbed into the circulatory system and transported around the body to various tissues, with 100% bio-availbility.
Distribution
Opioid distribution is highly dependent on specific properties of the opioid. To illicit desired effects, whether in clinical or recreational use, opioids target tissues in the central nervous system. To enter the brain and bind target receptors, opioids must cross the blood-brain-barrier. Opioids which are lipophilic more readily cross this barrier as they have a higher volume distribution, in addition to having a faster onset of action and a shorter duration of action. Opioid receptors are widely distributed around the body, and can be found in both the central nervous system (neuronal and non-neuronal tissues) and peripheral nervous system.
Metabolism
Opioids travel to the liver for metabolism via the hepatic portal vein. The opioids are then metabolized by cytochrome enzymes (specifically CYP 2D6 and 3A4) in glucoronidation reactions. A list of opioid substrates metabolized by liver cytochrome enzymes can be found below:
However, metabolism can often result in metabolites which are even more bio-active than their parent molecules (such as the metabolism of codeine to morphine). Highly active metabolites can significantly prolong the action of the opioid, even when the half-life has been exceeded. For example, the half-life of heroin is roughly 30 minutes, however the duration of action is 4 to 5 days, due to its highly active metabolites. Metabolism is also of particular relevance in considering drug-drug interactions, as any drug which interferes with the action of cytochrome enzymes (inducers or inhibitors) can reduce or enhance metabolism of opioids and produce subsequent toxicity.
Elimination
Opioid metabolites are primarily eliminated in urine via the kidneys. The half-life of opioid drug treatments are calculated to determine drug regime and rate of opioid titration, with steady state occurring after four half-lives. Health state of the liver and kidneys should be considered when prescribing opioids, as poor function of either can result in poor elimination and accumulation of opioids in tissues, producing toxicity.