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The UGT1A3*2 polymorphism affects atorvastatin lactonization and lipid-lowering effect in healthy volunteers

Objective We investigated whether the UGT1A3 polymorphisms play an important role in interindividual variations in atorvastatin lactonization and lipid-lowering effect. Methods Twenty-three healthy volunteers were administered atorvastatin 20 mg once daily for 14 days. Serum levels of lipids were measured before and 7, 13, 14, 15, 21, and 28 days after the initial dosing. Blood samples for pharmacokinetic analysis were collected up to 48 h after the last dose. Results The UGT1A3*2 and UGT1A1*28 polymorphism had a perfect linkage in the participants. Lactone formation was significantly higher in the UGT1A3*2 carriers. The areas under the curve of atorvastatin lactone and 2-hydroxyatorvastatin lactone were 72 and 160% higher in individuals with UGT1A3*2/*2 than UGT1A3*1/*1, respectively. The maximum percent decreases in the total and the low-density lipoprotein cholesterol from baseline in UGT1A3*2 carriers were 29 and 18% less than the UGT1A3*2 noncarriers, respectively. Conclusion The UGT1A3*2 polymorphism is correlated with increased atorvastatin lactonization and may affect its lipid-lowering effect.