Study On The Effect Of CYP1A2 Gene Polymorphism On The Pharmacokinetics Of Agomelatine

1 Objective1. Detection of the plasma concentration in healthy volunteers following oral administration of Agomelatine. 2. Through the genotyping method of CYP1A2polymorphism(rs762551) to research the relationship of antidepressant Agomelatine in vivo pharmacdynamic parameters and approach the causes of individual differences to do provide biological indicators in clinical individualized administration.2 Methods1 Establish a HPLC/MS/MS method for the determination of plasma concentrations after single-dose fasting oral administration of 25 mg Agomelatine tablet in male healthy volunteers 2. Adopting the Taq Man method to CYP1A2 gene polymorphism of rs762551 loci(168C/A) carry out genotyping. To set up the relationship of the genetype and concentration for study the high variation3 ResultsThe pharmacokinetic parameters Cmax, AUC0-8h, AUC0–∞ of the volunteers after a single dose fasting oral Agomelatine administration following as: rs762551C/C(n=36) homoygous for 30.851±18.267 ng / m L, 49.506±19.021 ng/m L·h,49.687±18.792 ng/m L·h; rs762551A/A(n=60) homozygous for 4.703±13.007 ng/m L,5.722±15.074 ng/m L·h, rs762551C/A(n=24) heterozygote for 19.821±14.321 ng/m L,31.681±16.342 ng/m L·h, 32.048 + 15.237 ng/m L·h.4 ConclusionsThe mean agomelatine AUC0–8h, AUC0–∞ and Cmax for the rs762551 CC homozygotes(n=36) was much higher than the rs762551 AA allele(n=60)(P<0.05) by the software of SPSS17.0 and DAS3.2.8. The rs762551 A genotype presented a significantly lower level of agomelatine exposure(AUC, Cmax) compared with the rs762551 C in Chinese healthy subjects. It suggested that the rs762551 genetic polymorphism might be associated with the marked interindividual variability ofagomelatine, and the pharmacokinetic profile of agomelatine may be different in different races.5 PerspectivesAdopt the Taq Man probe method to study the relationship of the plasma concentration and genotyping in 120 healthy male volunteers. It showed the pharmacokinetic parameters of the rs762551 C were much higher than rs762551 A. But we did not determinate the concentration and genotype in patients. In the future, we need to complement the research. And in-depth study of the other gene sites will affect the concentration of agomelatine.