Differences in Warfarin Pharmacodynamics and Predictors of Response Among Three Racial Populations

Background Population differences in warfarin dosing requirement have been reported; however, unlike the pharmacokinetics (PK) of warfarin, the quantitative influences of pharmacodynamic (PD) factors on the anticoagulation response to warfarin in different ethnic populations are totally unknown. Met...

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Bibliographic Details
Published in:Clinical pharmacokinetics 2019-08, Vol.58 (8), p.1077-1089
Main Authors: Ohara, Minami, Suzuki, Yasuhiko, Shinohara, Saki, Gong, Inna Y., Schmerk, Crystal L., Tirona, Rommel G., Schwarz, Ute I., Wen, Ming-Shien, Lee, Ming Ta Michael, Mihara, Kiyoshi, Nutescu, Edith A., Perera, Minoli A., Cavallari, Larisa H., Kim, Richard B., Takahashi, Harumi
Format: Article
Language:English
Subjects:
African Americans
Age
Algorithms
Creatinine
Ethnicity
Internal Medicine
Medicine
Medicine & Public Health
Minority & ethnic groups
Original Research Article
Pharmacodynamics
Pharmacokinetics
Pharmacology/Toxicology
Pharmacotherapy
Population
Racial differences
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Summary:Background Population differences in warfarin dosing requirement have been reported; however, unlike the pharmacokinetics (PK) of warfarin, the quantitative influences of pharmacodynamic (PD) factors on the anticoagulation response to warfarin in different ethnic populations are totally unknown. Methods Using population PK/PD analysis, we attempted to identify predictors of S -warfarin clearance [CL(S)] and half maximal effective concentration (EC 50 ) to quantify racial differences in both PK and PD parameters, and to assess the contribution of these parameters to the international normalized ratio (INR) and over-anticoagulation response (INR ≥ 4) in a cohort of 309 White, Asian and African American patients. Results Similar to our previous findings, the median CL(S) was 30% lower in African American patients than Asian and White patients (169 vs. 243 and 234 mL/h, p  A and/or factors associated with reduced CYP2C9 activity were more likely to have an INR ≥ 4. Conclusions Although there were contrasting racial differences in CL(S) and EC 50 that impacted on the INR, the racial difference in EC 50 was greater than that for CL(S), thus explaining the higher warfarin requirement for African American patients.
ISSN:0312-5963
1179-1926
DOI:10.1007/s40262-019-00745-5