What question did this study set out to answer?

To evaluate whether single nucleotide polymorphisms in drug transporter genes OATP-C (SLCO1B1), OATP-B, MRP2, and MDR1 influence the pharmacokinetics of pravastatin.

June 28, 2004Pharmacogenetics

High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1)

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To evaluate whether single nucleotide polymorphisms in drug transporter genes OATP-C (SLCO1B1), OATP-B, MRP2, and MDR1 influence the pharmacokinetics of pravastatin.
Sequenced the OATP-C gene and genotyped selected single nucleotide polymorphisms in OATP-B, MDR1, and MRP2 in 41 healthy Caucasian volunteers with prior pravastatin pharmacokinetic profiles.
Identified six outlier volunteers with unusually high pravastatin area under the curve (AUC) and performed comparative genotype and haplotype analyses against the remaining 35 subjects.
Carriers of the OATP-C 521TC and -11187GA genotypes exhibited a 106% (P = 0.0034) and 98% (P = 0.0061) higher mean pravastatin AUC0-12, respectively, compared to reference genotype carriers.
Mean pravastatin AUC0-12 was increased by 93% in carriers of the *15B haplotype (P = 0.024) and by 130% in carriers of the *17 haplotype (P = 0.0053) relative to non-carriers, whereas OATP-B, MRP2, and MDR1 variants showed no significant associations.

Authors

MNMikko NiemiGeneral / Preventive / Lipids ESElke SchaeffelerDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology TLThomas LangUniversity of Bremen

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Implication

Pharmacokinetic study reveals SLCO1B1 variants significantly increase pravastatin exposure in healthy volunteers, suggesting gene haplotypes dictate statin clearance.

Cite This Study

Niemi et al. (2004) studied this question.

synapsesocial.com/papers/6a1a4dcafebba9eb7c350656 https://doi.org/10.1097/01.fpc.0000114750.08559.32

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Implication

Pharmacokinetic study reveals SLCO1B1 variants significantly increase pravastatin exposure in healthy volunteers, suggesting gene haplotypes dictate statin clearance.

High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1)

Key Points

Discussion

Implication

Cite This Study

High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1)

Key Points

Discussion

Implication

Cite This Study

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