Role of active metabolites in the use of opioids

  title={Role of active metabolites in the use of opioids},
  author={Janet K. Coller and Lona Louring Christrup and Andrew Alexander Somogyi},
  journal={European Journal of Clinical Pharmacology},
The opioid class of drugs, a large group, is mainly used for the treatment of acute and chronic persistent pain. All are eliminated from the body via metabolism involving principally CYP3A4 and the highly polymorphic CYP2D6, which markedly affects the drug’s function, and by conjugation reactions mainly by UGT2B7. In many cases, the resultant metabolites have the same pharmacological activity as the parent opioid; however in many cases, plasma metabolite concentrations are too low to make a… 
Role of pharmacogenomics in pain therapy: Focus on opioids
Genetic factors might explain why some drugs 'don't work' or 'work too well' in routine clinical practice, including renal and liver function, co-morbidity and concomitant medications.
therapy: focus on opioids
Genetic factors might explain why some drugs 'don’t work' or 'work too well' in routine clinical practice, including renal and liver function, co-morbidity and concomitant medications.
The Pharmacogenetics of Opioid Pain Management
It is hypothesized that 20-40 percent of differences in patients with respect to drug response can be described by variations in a patient's phenotype, the observable traits that result from the genotype, which can include the patient's ability to metabolize drugs due to the expression of enzymesY.
Pharmacogenetics in Palliative Care
A major source of interpatient variability in response to these major palliative care classes of drugs can be attributed to the patients’ genetic profiles that control their drug metabolism, transport out of the brain and target site.
An update on analgesics.
  • I. Power
  • Biology, Medicine
    British journal of anaesthesia
  • 2011
It is clear that there is still much work to be done, but the need for highly efficacious analgesics with good side-effect profile remains.
Opioid metabolism and clinical aspects.
  • S. Mercadante
  • Medicine, Biology
    European journal of pharmacology
  • 2015
When administered orally, the test substance undergoes a long process of elimination, has the greatest tropism for the elimination organs and undergoes active biotransformation processes in the body of animals and, possibly, active metabolic products with an analgesic activity are formed.
Mechanistic and functional differentiation of tapentadol and tramadol
Tapentadol, a schedule-II controlled substance, is well-suited for pain conditions requiring a strong opioid component—and it has the benefit of greater gastrointestinal tolerability compared to classical strong opioids.
An Examination of the Complex Pharmacological Properties of the Non-Selective Opioid Receptor Modulator Buprenorphine
Buprenorphine’s characterization as only a partial mu-agonist is an oversimplification, and contemporary research shows the traditional explanation of the pharmacology of buprenorphines does not take into account changes to receptor theory, pharmacological terminology, route of administration, and biologically active major metabolites.
Modulation of Opioid Transport at the Blood-Brain Barrier by Altered ATP-Binding Cassette (ABC) Transporter Expression and Activity
Current knowledge on the transport of opioid analgesic drugs by ABC transporters at the blood-brain barrier is discussed, and a novel mechanism that can promote opioid-associated adverse drug events and development of addiction and tolerance is examined.


Pharmacogenetics of Opioids
The role of pharmacogenomics in mediating interpatient variability in efficacy and side effects to this important class of drugs will be better informed as knowledge regarding the interplay between genes affecting opioid pharmacokinetics including cerebral kinetics and pharmacodynamics increases.
Mu receptor binding of some commonly used opioids and their metabolites.
Loss of analgesic effect of morphine due to coadministration of rifampin
Drug therapy reviews: evaluation of butorphanol tartrate.
When administered intramuscularly or intravenously, butorphanol tartrate appears to be as effective for relieving moderate to severe pain as are pentazocine, meperidine and morphine.
Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplication
CYP2D6 genotypes predicting ultrarapid metabolism resulted in about 50% higher plasma concentrations of morphine and its glucuronides compared with the EM, and it might be good if physicians would know about the CYP2D 6 duplication genotype of their patients before administering codeine.
Pharmacological characterization of morphine-6 beta-glucuronide, a very potent morphine metabolite.
Results imply that morphine-6 beta-glucuronide elicited its analgesic actions through the same receptor mechanisms as morphine, which strongly suggests that this metabolite plays an important role in morphine's actions.
Paradoxical role of cytochrome P450 3A in the bioactivation and clinical effects of levo-alpha-acetylmethadol: importance of clinical investigations to validate in vitro drug metabolism studies.
CYP3A mediates human LAAM N-demethylation and bioactivation to norLAAM and dinorLAAM in vivo, which suggests a CYP3A-mediated metabolic pathway leading to inactive metabolites, which predominates over CYP 3A-dependent bioactivation.
Pharmacokinetics of methadone and its primary metabolite in 20 opiate addicts
In a closed metabolic ward the pharmacokinetics of methadone and its primary metabolite (EDDP) were studied in 20 long-term opiate addicts, and a poor correlation was found between the methad one dose and the steady-state level and the body clearance.
Pharmacokinetics and Pharmacodynamics of Seven Opioids in P-Glycoprotein-Competent Mice: Assessment of Unbound Brain EC50,u and Correlation of in Vitro, Preclinical, and Clinical Data
The results indicate that the mouse is a good model for opioid human brain disposition and clinical pharmacology and that superior in vitro-to-preclinical and preclinicalto-clinical correlations can be achieved with relevant unbound concentrations.