P. LenziniM. WadeliusS. KimmelJ. L. AndersonA. L. JorgensenM. PirmohamedM. D. CaldwellN. LimdiJ. K. BurmesterM. B. DowdP. NgchaisuksiriA. R. BssJ. ChenN. ErikssonA. RaneJ. D. LindhJ. F. CarlquistB. D. HorneG. GriceP. E. MilliganC. EbyJ. ShinH. KimD. KurnikC. M. SteinG. McMillinR. C. PendletonR. L. BergP. DeloukasB. F. GageWashington University in St. LouisUppsala UniversitetUniversity of PennsylvaniaIntermountain Medical CenterUniversity of LiverpoolMarshfield ClinicUniversity of AlabamaClinical Pharmacy Cardiac Risk ServiceMahidol UniversityHospital for Special Surgery - New YorkAkademiska SjukhusetKarolinska InstitutetSt. Louis College of PharmacyInje UniversityVanderbilt UniversityUniversity of UtahWellcome Trust Sanger Institute2018-09-242018-09-242010-05-01Clinical Pharmacology and Therapeutics. Vol.87, No.5 (2010), 572-57815326535000992362-s2.0-77951498679https://repository.li.mahidol.ac.th/handle/123456789/29698Well-characterized genes that affect warfarin metabolism (cytochrome P450 (CYP) 2C9) and sensitivity (vitamin K epoxide reductase complex 1 (VKORC1)) explain one-third of the variability in therapeutic dose before the international normalized ratio (INR) is measured. To determine genotypic relevance after INR becomes available, we derived clinical and pharmacogenetic refinement algorithms on the basis of INR values (on day 4 or 5 of therapy), clinical factors, and genotype. After adjusting for INR, CYP2C9 and VKORC1 genotypes remained significant predictors (P 0.001) of warfarin dose. The clinical algorithm had an R2of 48% (median absolute error (MAE): 7.0mg/week) and the pharmacogenetic algorithm had an R2of 63% (MAE: 5.5mg/week) in the derivation set (N = 969). In independent validation sets, the R2was 26-43% with the clinical algorithm and 42-58% when genotype was added (P = 0.002). After several days of therapy, a pharmacogenetic algorithm estimates the therapeutic warfarin dose more accurately than one using clinical factors and INR response alone.Mahidol UniversityMedicinePharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1038/clpt.2010.13