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Abstract: P492 NO DIFFERENCES IN THE SYSTEMIC EXPOSURE TO ATORVASTATIN BETWEEN ASIAN AND CAUCASIAN SUBJECTS
Poster - PHARMACOLOGY OF CVD - Safety of Lipid Modifying Agents Abstract: P492 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2
NO DIFFERENCES IN THE SYSTEMIC EXPOSURE TO ATORVASTATIN BETWEEN ASIAN AND CAUCASIAN SUBJECTS K Gandelman, M Messig, R Laskey Pfizer Inc, New York, NY Objectives: This analysis examined whether a pattern of increased exposure in Asian vs Caucasian populations is observed with atorvastatin. It has recently been shown that systemic exposure to rosuvastatin, the only statin contraindicated in Asian patients, is 2-fold higher among Asians than among Caucasians. It is unclear if this ethnic effect is a common phenomenon across the statin class. Methods: Pharmacokinetic data were analyzed from completed single dose (10-80 mg) studies in Asian and Caucasian subjects. AUC and Cmax values were dose normalized (AUCdn and Cmaxdn) by dividing each parameter by the dose from each study and further body weight normalized (AUCdn,wt and Cmaxdn,wt) by multiplying dose normalized values by mean body weight from each study. Study level means and standard deviations based on original scale data were combined and overall mean differences and 90% CIs for the differences, based on the t statistic, were expressed as ratios using Caucasians as the reference. Results: Data were analyzed from 321 Asians and 591 Caucasians from 23 studies (8 in Asian and 15 in Caucasian subjects). Dose normalized AUC and Cmax values were within the 80125% equivalent limits (Table). PK parameter AUCdn (ng.h/mL/mg) Cmaxdn (ng/mL/mg) AUCdn,wt (kg.ng.h/mL/mg) Cmaxdn,wt (kg.ng/mL/mg)
Asians (N=321) 2.34 0.39 155.92 25.79
Caucasians (n=591) 2.04 0.40 154.73 30.08
Ratio (%) 114.7 98.3 100.8 85.7
90% CI (%) 108.8-120.6 91.4-105.2 95.0-106.5 79.1-92.4
Conclusions: No differences were noted in the systemic exposure to atorvastatin between Asian and Caucasian subjects. Atorvastatin dosing does not therefore need to be adjusted in Asian patients based on pharmacokinetic considerations. Funding: Pfizer Inc.
NO DIFFERENCES IN THE SYSTEMIC EXPOSURE TO ATORVASTATIN BETWEEN ASIAN AND CAUCASIAN SUBJECTS K Gandelman, M Messig, R Laskey Pfizer Inc, New York, NY Objectives: This analysis examined whether a pattern of increased exposure in Asian vs Caucasian populations is observed with atorvastatin. It has recently been shown that systemic exposure to rosuvastatin, the only statin contraindicated in Asian patients, is 2-fold higher among Asians than among Caucasians. It is unclear if this ethnic effect is a common phenomenon across the statin class. Methods: Pharmacokinetic data were analyzed from completed single dose (10-80 mg) studies in Asian and Caucasian subjects. AUC and Cmax values were dose normalized (AUCdn and Cmaxdn) by dividing each parameter by the dose from each study and further body weight normalized (AUCdn,wt and Cmaxdn,wt) by multiplying dose normalized values by mean body weight from each study. Study level means and standard deviations based on original scale data were combined and overall mean differences and 90% CIs for the differences, based on the t statistic, were expressed as ratios using Caucasians as the reference. Results: Data were analyzed from 321 Asians and 591 Caucasians from 23 studies (8 in Asian and 15 in Caucasian subjects). Dose normalized AUC and Cmax values were within the 80125% equivalent limits (Table). PK parameter AUCdn (ng.h/mL/mg) Cmaxdn (ng/mL/mg) AUCdn,wt (kg.ng.h/mL/mg) Cmaxdn,wt (kg.ng/mL/mg)
Asians (N=321) 2.34 0.39 155.92 25.79
Caucasians (n=591) 2.04 0.40 154.73 30.08
Ratio (%) 114.7 98.3 100.8 85.7
90% CI (%) 108.8-120.6 91.4-105.2 95.0-106.5 79.1-92.4
Conclusions: No differences were noted in the systemic exposure to atorvastatin between Asian and Caucasian subjects. Atorvastatin dosing does not therefore need to be adjusted in Asian patients based on pharmacokinetic considerations. Funding: Pfizer Inc.