Pharmacogentics and pharmacokinetics – special focus on CYP2D6
25th October 14:00-16:00 at Lundbeck, Ottiliavej 9, 2500 Valby
14:00:14:50 40+ years with CYP2D6 – Kim Brøsen, Professor, Syddansk Universitet
14:50-15:10 Break with refreshments
15:10-16:00 Cytochrome P450 2D6 genotype-phenotype analyses for improved personalized medicine – Trine Frederiksen, Lundbeck and Syddansk Universitet
About Kim Brøsen
Kim Brøsen has been a towering presence within European clinical pharmacology for 35 years. He is internationally recognized as an innovative, pioneering and leading researcher within human drug metabolism and pharmacogenomics.
Kim Brøsen has been a strong developer and promoter of clinical pharmacology training and he has tirelessly pursued the implementation of clinical pharmacology as a medical specialty with a recognizable and respected professional identity. He has an elite publication record and resides deservedly among the Highly Cited Researchers within clinical pharmacology.
Kim Brøsen’s research has always been characterized by a deliberate and visible clinical approach in accordance with his position that clinical pharmacology as a medical specialty must strive to improve and support the medical treatment of patients. Kim Brøsen was among the true pioneers of pharmacogenomic research with numerous highly cited papers on the CYP2D6 polymorphism. Studies on imipramine metabolism and CYP2D6 polymorphism formed the basis of Kim Brøsen’s doctoral thesis in 1988. These studies resulted in one of his most important original discoveries that paroxetin is a strong in vivo inhibitor of CYP2D6 activity in humans. Kim Brøsen subsequently conducted a number of studies on the clinical relevance of CYP2D6 polymorphism to treatment with tricyclic antidepressants, especially imipramine and SSRIs, and opioids, especially codeine and tramadol. In recent years, Kim Brøsen has been increasingly involved in the role of drug transporters in human pharmacokinetics and -genomics. He is continuously providing substantial contributions to our understanding of the pharmacogenetics and -genomics of metformin, one of the most commonly prescribed antidiabetic drugs. Kim Brøsen has published more than 300 scientific papers as well as authored numerous national and international book chapters. He has been cited >13,500 times in the medical literature and has a CSI Hirsch Index of 66. Kim Brøsen has been the principal supervisor for more than 28 PhD students
About Trine Frederiksen
As part of her PhD research, Trine Frederiksen investigated CYP2D6 genotype-phenotype relationships for three different CYP2D6 substrates. PopPK models of the three compounds and their metabolites were developed based on data pooled from almost 50 clinical studies comprising more than 2,000 individuals in total. The CYP2D6-mediated metabolism was isolated and quantified for all individuals based on empirical Bayes estimates from the popPK models. The estimated CYP2D6 activity generally showed good agreement with subjects’ CYP2D6 genotype-predicted phenotype, but decreased function alleles were consistently associated with >50% reduction in enzyme activity, which is more than predicted by current CYP2D6 genotype-phenotype translation schemes. Furthermore, some CYP2D6 alleles appeared to exhibit substrate-specific enzyme activity warranting further investigation into this phenomenon. The findings from the project offer valuable new information to support ongoing discussions on optimizing CYP2D6 genotype-phenotype translation.