tedatioxetine (Lu AA24530) / Takeda, Lundbeck - LARVOL DELTA

Using population pharmacokinetic analyses of drugs metabolized by CYP2D6 to study the genotype-phenotype translation. (PubMed, Basic Clin Pharmacol Toxicol) - "We discuss population pharmacokinetics (popPK) as a tool for estimating CYP2D6 function and present findings from three popPK meta-analyses quantifying the impact of individual CYP2D6 alleles in the metabolism of vortioxetine, tedatioxetine and brexpiprazole. Moreover, the CYP2D6*2 allele exhibited reduced activity in the metabolism of brexpiprazole indicating substrate-specific behaviour. Considering the totality of evidence, the activity score system may be further refined to better reflect the enzyme function associated with these alleles."

Journal • PK/PD data • Review

Does ethnicity impact CYP2D6 genotype-phenotype relationships? (PubMed, Clin Transl Sci) - "The aim of this study was to investigate interethnic differences in CYP2D6 activity using clinical datasets of three CYP2D6 substrates: (i) brexpiprazole (N=476), (ii) tedatioxetine (N=500) and (iii) vortioxetine (N=1,073). Asian carriers of CYP2D6 decreased function alleles tended to exhibit higher CYP2D6 activity compared to Caucasians and African Americans. The observed interethnic differences within the CYP2D6 phenotype and genotype groups appeared to be driven by differences in CYP2D6 allele frequencies across ethnicities rather than interethnic differences in enzyme activity for individuals carrying identical CYP2D6 genotypes."

Journal

CYP2D6 Genotype-Phenotype Characterization Through Population Pharmacokinetic Modelling of Tedatioxetine. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Our findings suggest that the activity score assigned to the CYP2D6*41 should be revisited, while CYP2D6*17 appears to exhibit substrate-specific behaviour. Further studies are needed to confirm the findings and to improve the understanding of CYP2D6 genotype-phenotype relationships across substrates."

Clinical • Journal • PK/PD data