Pharmacodynamics +<unk>  (and metabolite) at opioid receptors Compound Affinities () Ratio Ref MOR:DOR:KOR<unk>  11.1 nM 962 nM 501 nM 1:87:45 Hydromorphone 0.47 nM 18.5 nM 24.9 nM 1:39:53 + Equianalgesic doses Compound Route Dose Codeine 200 mg<unk>  20–30 mg Hydromorphone 7.5 mg Hydromorphone 1.5 mg Morphine 30 mg Morphine 10 mg Oxycodone 20 mg Oxycodone 10 mg Oxymorphone 10 mg Oxymorphone 1 mg<unk>  is a highly selective full agonist of the μ-opioid receptor (MOR). This is the main biological target of the endogenous opioid neuropeptide β-endorphin.<unk>  has low affinity for the δ-opioid receptor (DOR) and the κ-opioid receptor (KOR), where it is an agonist similarly. Studies have shown<unk>  is stronger than codeine but only one-tenth as potent as morphine at binding to receptors and reported to be only 59% as potent as morphine in analgesic properties. However, in tests conducted on rhesus monkeys, the analgesic potency of<unk>  was actually higher than morphine. Oral<unk>  has a mean equivalent daily dosage (MEDD) factor of 0.4, meaning that 1 mg of<unk>  is equivalent to 0.4 mg of intravenous morphine. However, because of morphine's low oral bioavailability, there is a 1:1 correspondence between orally administered morphine and orally administered<unk> . The relative milligram strength of<unk>  to codeine is given as 6 fold, that is 5 mg has the effect of 30 mg of codeine; by way of the Roman numeral VI this is said to have given rise to the trade name Vicodin. Pharmacokinetics Absorption<unk>  is only pharmaceutically available as an oral medication. It is well-absorbed, but the oral bioavailability of<unk>  is only approximately 25%. The onset of action of<unk>  via this route is 10 to 20 minutes, with a peak effect (Tmax) occurring at 30 to 60 minutes, and it has a duration of 4 to 8 hours. Distribution The volume of distribution of<unk>  is 3.3 to 4.7 L/kg. The plasma protein binding of<unk>  is 20 to 50%. Metabolism In the liver,<unk>  is transformed into several metabolites, including norhydrocodone, hydromorphone, 6α-hydrocodol (dihydrocodeine), and 6β-hydrocodol. 6α- and 6β-hydromorphol are also formed, and the metabolites of<unk>  are conjugated (via glucuronidation).<unk>  has a terminal half-life that averages 3.8 hours (range 3.3–4.4 hours). The hepatic cytochrome P450 enzyme CYP2D6 converts<unk>  into hydromorphone, a more potent opioid (5-fold higher binding affinity to the MOR). However, extensive and poor cytochrome 450 CYP2D6 metabolizers had similar physiological and subjective responses to<unk> , and CYP2D6 inhibitor quinidine did not change the responses of extensive metabolizers, suggesting that inhibition of CYP2D6 metabolism of<unk>  has no practical importance. Ultra-rapid CYP2D6 metabolizers (1–2% of the population) may have an increased response to<unk> ; however,<unk>  metabolism in this population has not been studied. Norhydrocodone, the major metabolite of<unk> , is predominantly formed by CYP3A4-catalyzed oxidation. In contrast to hydromorphone, it is described as inactive. However, norhydrocodone is actually a MOR agonist with similar potency to<unk> , but has been found to produce only minimal analgesia when administered peripherally to animals (likely due to poor blood–brain barrier and thus central nervous system penetration). Inhibition of CYP3A4 in a child who was, in addition, a poor CYP2D6 metabolizer, resulted in a fatal overdose of<unk> . Approximately 40% of<unk>  metabolism is attributed to non-cytochrome P450-catalyzed reactions. Elimination<unk>  is excreted in urine, mainly in the form of conjugates.
Hydrocodone
Oxycodone
Noroxycodone
Norhydrocodone
Tramadol
Nefazodone
Morphine
Tapentadol