Pharmacogenomics: its role in re-establishing coumarin as treatment for lymphedema.
Although there remains some significant controversy regarding the use and benefits of coumarin (5,6-benzo-alpha pyrone), it would seem that targeted appropriate and monitored use of the drug does have a significant role in the treatment of lymphedemas. The particular benefits are its cost and ease of administration. Given today's demands for high level investigative clinical trials, it would be virtually impossible to conduct a study large enough to make any significant conclusions about hepatotoxic effects. However, it seems without doubt that the majority of studies conducted thus far suggest that coumarin (and other benzopyrones, i.e., the ruto-sides, which do not have hepatotoxic effects and which are often discussed in aggregate with coumarin) is effective in treating lymphedema, particularly when used in conjunction with complex physical therapy. The use of pharmacogenomics could significantly lower the risk of coumarin-associated hepatotoxicity, by targeting the use of coumarin to those with functional CYP2A6. Further research in this area will be required to re-evaluate the cost- benefit ratio and to determine the potential for the reintroduction of coumarin as a potent treatment for lymphedema. The perceived negative image of coumarin should not be allowed to carry across to the other benzopyrones, as they still confer a significant benefit in the management of lymphedemas.
Farinola
Nicholas
N
Lymphedema Assessment Clinic, Department of Surgery, School of Medicine, Flinders University and Flinders Medical Centre, Adelaide, South Australia.
Piller
Neil
N
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D003374:Coumarins / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D065637:Cytochrome P-450 CYP2A6; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D008209:Lymphedema / Q000188:drug therapy* / Q000235:genetics; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide
D003374:Coumarins; D005419:Flavonoids; C030123:coumarin; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6