"Furthermore, once a patient has been identified as a 'poor metaboliser', this means that other drugs that are also metabolised via CYP2D6 will be less effective, such as codeine and, to a lesser extent, oxycodone, and so this knowledge will help clinicians to decide on alternative treatment strategies for their patients," Varin added.
"However, in about 5-10 percent of Caucasian patients the CYP2D6 enzyme is inefficient and does not produce enough ODT to bind effectively to the opioid receptors; these patients are known as 'poor metabolisers' and will have poorly controlled pain unless the problem is identified quickly and they are switched to morphine or nefopam," he said.
* Two variant genes [right arrow] poor metaboliser.
(3) For drugs inactivated by the CYP enzymes, poor metabolisers will be slow to clear the drug and risk toxicity, while ultrafast metabolisers will clear the drug too rapidly and may not achieve therapeutic plasma concentrations (see box 1, p22).
(16) Poor metabolisers
(occurring most frequently in Europeans at five to 10 per cent of the population) may convert little codeine, so for them this drug is an ineffective form of analgesia.
Likewise, poor metabolisers
(PM) may need lower dose because the drug will not easily be removed from blood stream than normal.
Quite a few research studies have shown that breast cancer patients treated with adjuvant tamoxifen and have reduced CYP2D6 enzymatic activity due to genetic polymorphisms or drug interactions may have an increased risk of recurrence and shortened disease-free survival.6 Depending upon the activity of the enzyme and the combinations of the alleles, individuals are classified as poor metabolisers
(PMs), intermediate metabolisers (IMs), extensive metabolisers (EMs) and ultra-extensive metabolisers (UMs) of CYP2D6 substrates.
The potential study participants were genotyped by PAREXEL to identify nearly 400 poor metabolisers
of Cytochrome P450 2D6 (CYP2D6), an enzyme involved in the metabolism of drugs.
Genotyping of poor metabolisers
of debrisoquine by allele-specific PCR amplification.
Colour is thought to show your constitutional leanings: so the brown- eyed, for example, tend to be poor metabolisers
of fats; the blue-eyed are liable to develop acid conditions such as arthritis; while those with mixed irises tend to suffer poor digestion.
As well as age-related changes in metabolic processes, there are segments of the population who may unknowingly be genetically poor metabolisers
for particular drug metabolism pathways, with the result that drug dosage should be reduced to avoid adverse effects.
Metabolic disposition of proguanil in extensive and poor metabolisers
of Smephenytoin 4'-hydroxylation recruited from an Indonesian population.