ORGANIC ANION–TRANSPORTING POLYPEPTIDES - Drug Transporters: Molecular Characterization and Role in Drug Disposition - page 90

TABLE 5.5. SLCO1B1 Genotype and Pharmacokinetics

PK Effect in

SLCO1B1 Comparison with

Drug Genotype Ethnicity Reference Genotype a Ref.

∗ 15/ ∗ 15

Pravastatin Asian AUC ↑ 187% 69

∗ 1a/ ∗ 5

Caucasian AUC ↑ 143% 70

∗ 1b/ ∗ 1b

Caucasian AUC ↓ 40% 70

∗ 17/ ∗ 17

Caucasian AUC ↑ 130% 71

∗ 1b/ ∗ 1b

Asian AUC ↓ 35% 75

∗ 5, ∗ 15, ∗ 17
variant
haplotype

Caucasian AUC ↑ 110% 89

∗ 15/ ∗ 15

↑

Caucasian,
African
American

AUC 92 % unpublished

Rosuvastatin 521CC Caucasian AUC ↑ 217% 77

Pitavastatin Asian AUC ↑ % 76

Repaglinide 521CC Caucasian AUC ↑ 188% 78

Nateglinide 521CC Asian AUC ↑ 108% 79

Atrasentan Low-activity

genotype

Caucasian,
non-caucasian

AUC ↑ 73% 81

Valsartan

∗ 1b/ ∗ 1b

Asian AUC ↓ 27% 75

Fexofenadine 521CC Caucasian AUC ↑ 127% 80

∗ 15 carriers

Irinotecan Asian AUC ↑ 182% 82

∗ 15 carriers

Ezetimibe-
glucuronide

Caucasian AUC ↑ 305% 83

a Reference genotype, SLCO1B1 ∗ 1a.

in children with heterozygous familial hypercholesterolemia. 84 Children with the
SLCO1B1 521C genotype had lower pravastatin plasma levels than those with 521T.
This trend goes in the opposite direction to that seen in adults and highlights the
complexities of understanding SLCO1B1 genotype-phenotype relationships.
With the understanding that HMG-CoA reductase inhibitor drug levels are some-
what determined by genetics, there has been interest in assessing whether SLCO1B1
genotype also predicts risk for muscle toxicity and cholesterol lowering effect. It
is reported that that increased drug dose is a risk factor for HMG-CoA reductase
inhibitor-mediated myopathies including severe rhabdomyolysis. 85 suggesting that
enhanced drug exposure resulting from SLCO1B1 genetics similarly elevates risk for
such side effects. 86 In the case of atorvastatin, SCLO1B1 polymorphisms were not
different in patients who did or did not experience myopathy. 87 Because OATP1B1
presents HMG-CoA reductase inhibitor drugs to their target in hepatocytes, investiga-
tors have examined the role of transporter genetics and the pharmacological effects.
In one study, patients with the SLCO1B1 521C genotype had reduced lipid lowering
effect by statin drugs than those carrying 521T. 88 By contrast, there was a lack of influ-
ence of SLCO1B1 genotype to the lipid lowering of pravastatin in two studies despite