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Rasagiline is a selective and irreversible inhibitor of monoamine oxidase type B with neuroprotective effect, indicated for the management of Parkinson’s disease. The aim of this work was to evaluate the impact of seven <i>CYP1A2</i> alleles and of 120 additional variants located in other CYP enzymes (e.g., <i>CYP2C19</i>), UGT enzymes (e.g., <i>UGT1A1</i>) or other enzymes (e.g., <i>NAT2</i>), and transporters (e.g., <i>SLCO1B1</i>) on the pharmacokinetic variability and safety of rasagiline. A total of 118 healthy volunteers enrolled in four bioequivalence clinical trials consented to participate in this pharmacogenetic study. <i>CYP1A2</i> alleles were not associated with the pharmacokinetic variability of rasagiline. Patients with <i>ABCB1</i> rs1045642 G/A+A/A genotypes presented higher area under the curve adjusted by dose per weight (AUC_0-∞/DW) than those with the G/G genotype (<i>p</i> = 0.012) and lower volume of distribution (V_d/F) and clearance (Cl/F) (<i>p</i> = 0.001 and <i>p</i> = 0.012, respectively). Subjects with the <i>ABCC2</i> rs2273697 A/A genotype presented lower t_max (i.e., the time to reach the maximum concentration, C_max) compared to those with G/G+G/A genotypes (<i>p</i> = 0.001). Volunteers with the <i>SLC22A1</i> *1/*5 genotype exhibited lower C_max/DW and higher t_max (<i>p</i> = 0.003 and <i>p</i> = 0.018, respectively) than subjects with the *1/*1 diplotype. Only one adverse drug reaction was reported: headache. Our results suggest the genetic polymorphism of drug transporters, rather than metabolizing enzymes, conditions the pharmacokinetics of rasagiline.