SLCO1B1 polymorphism markedly affects the pharmacokinetics of lovastatin acid.

Article Details

Citation

Copy to clipboard

Tornio A, Vakkilainen J, Neuvonen M, Backman JT, Neuvonen PJ, Niemi M

SLCO1B1 polymorphism markedly affects the pharmacokinetics of lovastatin acid.

Pharmacogenet Genomics. 2015 Aug;25(8):382-7. doi: 10.1097/FPC.0000000000000148.

PubMed ID

26020121 [ View in PubMed

]

Abstract

OBJECTIVE: Organic anion transporting polypeptide 1B1 (OATP1B1, encoded by SLCO1B1 gene) is a hepatic uptake transporter, and its genetic variability is associated with pharmacokinetics and muscle toxicity risk of simvastatin. We examined the possible effects of variations in the SLCO1B1 gene on the pharmacokinetics of lovastatin in a prospective genotype panel study. PARTICIPANTS AND METHODS: Seven healthy volunteers with the SLCO1B1*1B/*1B genotype, five with the SLCO1B1*5/*15 or *15/*15 genotype, and 15 with the SLCO1B1*1A/*1A genotype (controls) were recruited. Each study participant ingested a single 40-mg dose of lovastatin. Plasma concentrations of lovastatin (inactive lactone) and its active metabolite lovastatin acid were measured up to 24 h. RESULTS: In the SLCO1B1*5/*15 or *15/*15 genotype group, the geometric mean Cmax and AUC0-24 of lovastatin acid were 340 and 286% of the corresponding values in the SLCO1B1*1A/*1A (reference) genotype group (P<0.005). In contrast, the AUC0-24 of lovastatin acid in the SLCO1B1*1B/*1B genotype group was only 68% of that in the reference genotype group (P=0.03). No statistically significant association was observed between the SLCO1B1 genotype and the pharmacokinetics of lovastatin lactone. CONCLUSION: SLCO1B1*5/*15 and *15/*15 genotypes markedly increase the exposure to active lovastatin acid, but have no significant effect on lovastatin lactone, similar to their effects on simvastatin and simvastatin acid. Accordingly, it is probable that the risk of muscle toxicity during lovastatin treatment is increased in individuals carrying the SLCO1B1*5 or *15 allele. The SLCO1B1*1B/*1B genotype is associated with reduced lovastatin acid concentrations, consistent with enhanced hepatic uptake.

DrugBank Data that Cites this Article

Drugs

Lovastatin

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Lovastatin	Solute carrier organic anion transporter family member 1B1	Protein	Humans	Unknown	Substrate Inhibitor	Details