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GW24-e2267 Atorvastatin decrease the active thiol metabolite of clopidogrel When It Is Administered Concomitantly in healthy Chinese volunteers
  1. Gao Yan1,
  2. Fan Li2
  1. 1Third Department of Cadre Ward, General Hospital of Jinan Military Region, Shifan Road 25, Jinan 250031 China
  2. 2First Geriatric Cardiology Division, Chinese PLA General Hospital, Fuxing Road 28, Beijing 100853 China

Abstract

Objectives To investigate whether co-administration of atorvastatin with clopidogrel affect active thiol metabolite of clopidogrel in healthy Chinese volunteers

Methods This was a randomized, open, crossover study, with a 4-week washout period. In enrolled 24 healthy volunteers, 23 completed the experiment. 12 patients in each group were treated with clopidogrel 75mg for 1weeks or atorvastatin 40mg plus clopidogrel 75mg for 1 week, after a 4-week washout period, they received the alternative drug. Blood samples for pharmacokinetic assessments were collected. Concentrations of the active metabolite of clopidogrel were measured using a validated LC-MS/MS method.

Results Twenty three of the 24 enrolled subjects completed the study (mean (SD) age 50 (10) years and a mean body weight of 60 (7) kg). The plasma concentrations of clopodogrel were significantly reduced by combined with atorvastatin, the AUC0_∝ of clopidogrel active metabolite decreased in 20 subjects, the AUC0_∝ values were decreased by >30% in 6 subjects and 20% ∼30% in 5 subjects. The mean AUC0_∝ of clopidogrel active metabolite in clopidogrel group was 83.12%(19.63 ± 6.32 vs 23.62 ± 7.65 ng/ml·h-1, p<0.01) of clopidogrel plus atorvastatin group. There was no statistically difference in t1/2 (0.54 ± 0.19 VS 0.53 ± 0.21. P = 0.78). the Cmax (20.04 ± 8.20 VS 16.84 ± 5.85, P = 0.005) and oral clearance (3.67 ± 1.49 VS 4.34 ± 1.99, P = 0.002) of clopidogrel active metabolite were significantly affected by coadministration of atorvastatin.

Conclusions The pharmacokinetics parameters of clopidogrel active metabolite were significantly decreased by coadministration of atorvastatin.

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