1 (ESM) for a histogram of measured concentrations Table 4 Comparison of ABCB1 and CES1 genotype and allele frequencies of 52 patients on dabigatran etexilate with Caucasians included in the CEUa dataset Gene (SNP) Allele change Genotype, n (frequency) Minor allele MAF, n (%) HWE, p value MAF (CEU), p value ABCB1 (rs4148738)

CHIR-99021 cost T>C T/T 13 (0.250) C/T 31 (0.596) C/C 8 (0.154) C 0.45 0.14 0.48 ABCB1 (rs1045642) C>T T/T 16 (0.308) C/T 26 (0.500) C/C 10 (0.192) C 0.44 0.92 0.43 CES1 (rs2244613) T>G T/T 38 (0.731) G/T 12 (0.231) G/G 2 (0.038) G 0.15 0.41 0.15 CES1 (rs4122238) C>T C/C 40 (0.769) C/T 12 (0.231) T/T 0 T 0.12 0.35 0.12 CES1 (rs8192935) A>G G/G 27 (0.519) A/G 23 (0.442) A/A 2 (0.038) A 0.26 0.28 0.31 HWE Hardy–Weinberg equilibrium, MAF minor Fulvestrant concentration allele frequency, SNP single nucleotide polymorphism aUtah residents with ancestry from northern and western Europe (CEU) (http://​snp.​cshl.​org/​citinghapmap.​html.​en) 3.1 Correlation Between GFR Equations and Dabigatran Concentrations The log-transformed dabigatrantrough values were found to be normally distributed (p = 0.98).

Of the published non-renal covariates (Table 1), only the concomitant use of the P-gp inducers phenytoin and phenobarbitone explained a significant portion of the variability in dabigatrantrough values between the 52 patients (p = 0.012, Supplementary

Table 1, electronic supplementary material [ESM]). Administration of phenytoin and phenobarbitone occurred in a single individual prescribed dabigatran etexilate 110 mg twice daily who had a low trough plasma dabigatran concentration of 9 µg/L (dabigatrantrough = 0.04 µg/L per mg/day, z-score of the log-transformed dabigatrantrough = −3.25). This individual had been electively admitted Aprepitant for sleep studies, and the blood samples were taken on the fourth day of his stay as an inpatient. His hospital prescription chart revealed that dabigatran etexilate was administered to him throughout the admission (total of 6 doses) as per his aforementioned prescribed dose rate. A multiple linear regression model was constructed consisting of this covariate, as well as the presence of concomitant proton-pump inhibitors [11, 12], concomitant P-gp inhibitors (verapamil and amiodarone) [5, 7] and three CES1 SNPs (rs8192935, rs2244613 and rs4122238) [13]. The multiple linear regression model that included these covariates had an unadjusted R 2 of 0.29 for the z-scores of the log-transformed dabigatrantrough. The R 2 values of the four renal function equations for the standardised residuals of the multiple linear regression model are presented in Table 5.