Extensive metaboliser

It is becoming increasingly common to see pharmacogenomics used in clinical decision-making.

CYP2D6 may be responsible (at least in part) for metabolism of about one quarter of medications. Recently, there have been patient deaths highlighted in the Canadian media that have been attributed to use of codeine in ultra-rapid metabolisers. One report described the death of a pediatric patient receiving normal codeine doses post-tonsillectomy and another involved the breastfed infant of a mother who was taking codeine post-partum. Not all issues affecting rapid metabolisers are so shocking or tragic; patients that take ondansetron for the prevention of chemotherapy-induced nausea and vomiting may simply find the drug to be ineffective, and would benefit from rotation to another 5-HT₃ antagonist such as granisetron that is not metabolised by CYP2D6.

In some children’s hospitals in North America, pharmacogenomic testing for CYP2D6 and other metabolic enzyme variants is now routine. Pediatric patients with acute lymphoblastic leukemia (ALL) receive the thiopurine drug mercaptopurine for maintenance therapy.  Mercaptopurine is dosed to maintain a suppressed absolute neutrophil count (ANC) within a target range. The drug is metabolised by the enzyme thiopurine methyltransferase (TPMT), the product of a polymorphic gene, with a small number (<1%) of people expressing a TPMT enzyme devoid of activity, and around 10% of patients having a heterozygous variant that has intermediate activity. Testing for TMPT genotype is now quite readily available, and patients diagnosed with ALL may either be tested for the variant upon diagnosis, or if they experience excessive bone marrow suppression after starting a standard dosing regimen of mercaptopurine.