The DOI matches its Crossref record; 83 of the 83 references it cites were found in a registry or an index.
SLCO1B1 polymorphism markedly affects the pharmacokinetics of lovastatin acid
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.
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Self-citationSLCO1B1 Variants and Statin-Induced Myopathy — A Genomewide Study
(2008) · New England Journal of Medicine · doi:10.1056/nejmoa0801936 · Cited by 2,043
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Cited by
Membrane transporters in drug development
The International Transporter Consortium, Giacomini, K. M., Huang, S.-M., Tweedie, D. J., Benet, L. Z., Brouwer, K. L. R., Chu, X., Dahlin, A., Evers, R., Fischer, V., et al. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3028 · Cited by 3,340
Self-citationDifferent Effects of SLCO1B1 Polymorphism on the Pharmacokinetics of Atorvastatin and Rosuvastatin
Pasanen, M. K., Fredrikson, H., Neuvonen, P. J., & Niemi, M. (2007) · Clinical Pharmacology & Therapeutics · doi:10.1038/sj.clpt.6100220 · Cited by 432
Self-citationDeGorter, M. K., Tirona, R. G., Schwarz, U. I., Choi, Y.-H., Dresser, G. K., Suskin, N., Myers, K., Zou, G., Iwuchukwu, O., Wei, W.-Q., et al. (2013) · Circulation: Cardiovascular Genetics · doi:10.1161/circgenetics.113.000099 · Cited by 195
Enteric Microbiome Metabolites Correlate with Response to Simvastatin Treatment
Kaddurah-Daouk, R., Baillie, R. A., Zhu, H., Zeng, Z.-B., Wiest, M. M., Nguyen, U. T., Wojnoonski, K., Watkins, S. M., Trupp, M., & Krauss, R. M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025482 · Cited by 193
Keskitalo, J. E., Pasanen, M. K., Neuvonen, P. J., & Niemi, M. (2009) · Pharmacogenomics · doi:10.2217/pgs.09.85 · Cited by 189
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Metadata
- Authors
- Tornio, A., Vakkilainen, J., Neuvonen, M., Backman, J. T., Neuvonen, P. J., & Niemi, M.
- Venue
- Pharmacogenetics and Genomics
- Published
- 2015-08
- Volume
- 25
- Issue
- 8
- Pages
- 382-387
- ISSN
- 1744-6872 (ISSN-L)
- OpenAlex
- W2156173568
- Cited by
- 409
- References
- 83
- FWCI
- 33.64
- Type
- journal article
- Language
- en
- Open access
- closed
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