Identification of the Effect of Multiple Polymorphisms on the Pharmacokinetics of Simvastatin and Simvastatin Acid Using a Population-Modeling Approach
Abstract
The aim of this work was to develop a joint population pharmacokinetic model for simvastatin (SV) and its active metabolite, simvastatin acid (SVA), that incorporates the effects of multiple genetic polymorphisms and clinical/demographic characteristics. SV/SVA plasma concentrations, demographic/clinical data, and genotypes for 18 genetic variants were collected from 74 individuals (three clinical trials) and analyzed using a nonlinear mixed-effects modeling approach. The structural model that best described the data included a two- and a one-compartment disposition model for SV and SVA, respectively. Age, weight, Japanese ethnicity, and seven genetic polymorphisms-rs4149056 (SLCO1B1), rs776746 (CYP3A5), rs12422149 (SLCO2B1), rs2231142 (ABCG2), rs4148162 (ABCG2), rs4253728 (PPARA), and rs35599367 (CYP3A4)-were identified as significantly affecting model parameters. The developed model was used to assess combinations of these covariates, highlighting specific risk factors associated with altered SV/SVA pharmacokinetics, and consequently myopathy cases that cannot be solely attributed to the rs4149056 CC genotype.
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Several DGI studies describe an association between SVL disposition and BCRP transporter polymorphisms, but findings are inconsistent and the clinical importance is still highly debatable.
“Although several DGI studies describe an association between SVL disposition and BCRP transporter polymorphisms, 29 , 30 , 34 , 36 findings are inconsistent and the clinical importance is still highly debatable.”
From Does the choice of applied physiologically‐based pharmacokinetics platform matter? A case study on simvastatin disposition and drug–drug interaction (2022) · cites this paper as [34]
Cites
dbSNP: the NCBI database of genetic variation
Sherry, S. T. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.1.308 · Cited by 7,502 · see citing works
Regulation of the mevalonate pathway
Goldstein, J. L., & Brown, M. S. (1990) · Nature · doi:10.1038/343425a0 · Cited by 5,394 · see citing works
<i>SLCO1B1</i> Variants and Statin-Induced Myopathy — A Genomewide Study
(2008) · New England Journal of Medicine · doi:10.1056/nejmoa0801936 · Cited by 2,043 · see citing works
Mangoni, A. A., & Jackson, S. H. (2003) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.2003.02007.x · Cited by 1,887 · see citing works
Thompson, P. D., Clarkson, P., & Karas, R. H. (2003) · JAMA · doi:10.1001/jama.289.13.1681 · Cited by 1,463 · see citing works
Ways to Fit a PK Model with Some Data Below the Quantification Limit
Beal, S. L. (2001) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1023/a:1012299115260 · Cited by 1,116 · see citing works
Niemi, M., Pasanen, M. K., & Neuvonen, P. J. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.002857 · Cited by 636 · see citing works
Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs
Wang, D., Guo, Y., Wrighton, S. A., Cooke, G., & Sadée, W. (2010) · The Pharmacogenomics Journal · doi:10.1038/tpj.2010.28 · Cited by 507 · see citing works
Self-citationLEE, E., RYAN, S., Birmingham, B. K., Zalikowski, J. A., March, R. E., Ambrose, H., MOORE, R., Lee, C. G. L., CHEN, Y., & Schneck, D. W. (2005) · Clinical Pharmacology & Therapeutics · doi:10.1016/j.clpt.2005.06.013 · Cited by 480 · see citing works
SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid
Pasanen, M. K., Neuvonen, M., Neuvonen, P. J., & Niemi, M. (2006) · Pharmacogenetics and Genomics · doi:10.1097/01.fpc.0000230416.82349.90 · Cited by 470 · see citing works
SLCO1B1 polymorphism markedly affects the pharmacokinetics of lovastatin acid
Tornio, A., Vakkilainen, J., Neuvonen, M., Backman, J. T., Neuvonen, P. J., & Niemi, M. (2015) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0000000000000148 · Cited by 410 · see citing works
Glucuronidation of Statins in Animals and Humans: A Novel Mechanism of Statin Lactonization
Prueksaritanont, T., Subramanian, R., Fang, X., Ma, B., Qiu, Y., Lin, J. H., Pearson, P. G., & Baillie, T. A. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.5.505 · Cited by 344 · see citing works
Wilke, R. A., Ramsey, L. B., Johnson, S. G., Maxwell, W. D., McLeod, H. L., Voora, D., Krauss, R. M., Roden, D. M., Feng, Q., Cooper‐DeHoff, R. M., et al. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.57 · Cited by 332 · see citing works
Transporter Pharmacogenetics and Statin Toxicity
Niemi, M. (2009) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2009.197 · Cited by 329 · see citing works
(1997) · PubMed · Cited by 271 · see citing works
Nies, A. T., Niemi, M., Burk, O., Winter, S., Zanger, U. M., Stieger, B., Schwab, M. G., & Schaeffeler, E. (2013) · Genome Medicine · doi:10.1186/gm405 · Cited by 268 · see citing works
Metabolic disposition studies on simvastatin, a cholesterol-lowering prodrug.
Vickers, S., Duncan, C. A., Chen, I. W., Rosegay, A., & Duggan, D. E. (1990) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)07595-6 · Cited by 246 · see citing works
Human skeletal muscle drug transporters determine local exposure and toxicity of statins
Knauer, M. J., Urquhart, B. L., Meyer zu Schwabedissen, H. E., Schwarz, U. I., Lemke, C. J., Leake, B. F., Kim, R. B., & Tirona, R. G. (2010) · Circulation Research · doi:10.1161/circresaha.109.203596 · Cited by 222 · see citing works
Grube, M., Köck, K., Oswald, S., Draber, K., Meissner, K., Eckel, L., Böhm, M., Felix, S. B., Vogelgesang, S., & Jedlitschky, G. (2006) · Clinical Pharmacology & Therapeutics · doi:10.1016/j.clpt.2006.09.010 · Cited by 215 · see citing works
Elsby, R., Hilgendorf, C., & Fenner, K. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.163 · Cited by 198 · see citing works
Keskitalo, J. E., Pasanen, M. K., Neuvonen, P. J., & Niemi, M. (2009) · Pharmacogenomics · doi:10.2217/pgs.09.85 · Cited by 189 · see citing works
Clinical Pharmacokinetics and Practical Applications of Simvastatin
Mauro, V. F. (1993) · Clinical Pharmacokinetics · doi:10.2165/00003088-199324030-00002 · Cited by 187 · see citing works
Prueksaritanont, T., Ma, B., & Yu, N. (2003) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.2003.01833.x · Cited by 180 · see citing works
Power, Selection Bias and Predictive Performance of the Population Pharmacokinetic Covariate Model
Ribbing, J., & Jonsson, E. N. (2004) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1023/b:jopa.0000034404.86036.72 · Cited by 172 · see citing works
In vitro and in vivo biotransformation of simvastatin, an inhibitor of HMG CoA reductase.
Vickers, S., Duncan, C. A., Vyas, K. P., Kari, P. H., Arison, B. H., Prakash, S. R., Ramjit, H. G., Pitzenberger, S. M., Stokker, G. E., & Duggan, D. E. (1990) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)08543-5 · Cited by 154 · see citing works
PPARA: A Novel Genetic Determinant of CYP3A4 In Vitro and In Vivo
Klein, K., Thomas, M., Winter, S., Nussler, A. K., Niemi, M., Schwab, M. G., & Zanger, U. M. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2011.336 · Cited by 153 · see citing works
Keskitalo, J. E., Kurkinen, K. J., Neuvonen, P. J., & Niemi, M. (2008) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2008.25 · Cited by 148 · see citing works
Elens, L., Becker, M. L., Haufroid, V., Albert Hofman, D., Visser, L. E., Uitterlinden, A. G., Stricker, B. H. C., & van Schaik, R. H. N. (2011) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e32834c6edb · Cited by 114 · see citing works
Kim, K., Park, P., Lee, O., Kang, D., & Park, J. Y. (2006) · The Journal of Clinical Pharmacology · doi:10.1177/0091270006295063 · Cited by 102 · see citing works
Use of Transporter Knockdown Caco-2 Cells to Investigate the In Vitro Efflux of Statin Drugs
Li, J., Volpe, D. A., Wang, Y., Zhang, W., Bode, C., Owen, A. J., & Hidalgo, I. J. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.038075 · Cited by 97 · see citing works
Pharmacogenetic profiling across the irinotecan pathway in Asian patients with cancer
Zhou, Q. S., Sparreboom, A., Tan, E.-H., Cheung, Y., Lee, A., Poon, D. Y. H., Lee, E. J. D., & Chowbay, B. (2005) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2004.02330.x · Cited by 94 · see citing works
Tomita, Y., Maeda, K., & Sugiyama, Y. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.221 · Cited by 88 · see citing works
Cheng, H., Rogers, J. D., Sweany, A. E., Dobrinska, M. R., Stein, E. A., Tate, A. C., Amin, R. D., & Quan, H. (1992) · Pharmaceutical Research · doi:10.1023/a:1015828811865 · Cited by 57 · see citing works
Kim, J., Ahn, B., Chae, H., Han, S., Doh, K., Choi, J., Jun, Y. K., Lee, Y. W., & Yim, D. (2011) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/j.1742-7843.2011.00700.x · Cited by 43 · see citing works
Bertrand, J., Comets, E., & Mentré, F. (2008) · Journal of Biopharmaceutical Statistics · doi:10.1080/10543400802369012 · Cited by 41 · see citing works
Interconversion Pharmacokinetics of Simvastatin and its Hydroxy Acid in Dogs: Effects of Gemfibrozil
Prueksaritanont, T., Qiu, Y., Mu, L., Michel, K., Brunner, J., Richards, K. M., & Lin, J. H. (2005) · Pharmaceutical Research · doi:10.1007/s11095-005-6037-2 · Cited by 35 · see citing works
Bertrand, J., Comets, E., Laffont, C. M., Chenel, M., & Mentré, F. (2009) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-009-9124-x · Cited by 34 · see citing works
Bertrand, J., & Balding, D. J. (2013) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e32835dd22c · Cited by 20 · see citing works
Lehr, T., Schaefer, H.-G., & Staab, A. (2010) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e32833b747f · Cited by 12 · see citing works
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Membrane transporters in drug development and as determinants of precision medicine
Galetin, A., Brouwer, K. L. R., Tweedie, D., Yoshida, K. J., Sjöstedt, N., Aleksunes, L. M., Chu, X., Evers, R., Hafey, M. J., Lai, Y., et al. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00877-1 · Cited by 246 · see citing works
Self-citationChu, X., Liao, M., Shen, H., Yoshida, K. J., Zur, A. A., Arya, V., Galetin, A., Giacomini, K. M., Hanna, I. H., Kusuhara, H., et al. (2018) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1216 · Cited by 209 · see citing works
Self-citationTurner, R. M., & Pirmohamed, M. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm9010022 · Cited by 201 · see citing works
An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins
Hirota, T., Fujita, Y., & Ieiri, I. (2020) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2020.1801634 · Cited by 190 · see citing works
Drug–drug–gene interactions and adverse drug reactions
Malki, M. A., & Pearson, E. R. (2019) · The Pharmacogenomics Journal · doi:10.1038/s41397-019-0122-0 · Cited by 169 · see citing works
Lai, Y., Chu, X., Di, L., Gao, W., Guo, Y., Liu, X., Lu, C., Mao, J., Shen, H., Tang, H., et al. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.03.009 · Cited by 169 · see citing works
Self-citationKell, D. B., & Oliver, S. G. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00231 · Cited by 155 · see citing works
Yee, S. W., Brackman, D. J., Ennis, E. A., Sugiyama, Y., Kamdem, L. K., Blanchard, R. L., Galetin, A., Zhang, L., & Giacomini, K. M. (2018) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1098 · Cited by 143 · see citing works
Self-citationLee, C. A., O'Connor, M., Ritchie, T. K., Galetin, A., Cook, J., Ragueneau, I., Ellens, H. M., Feng, B., Taub, M. E., Paine, M. F., et al. (2015) · Drug Metabolism and Disposition · doi:10.1124/dmd.114.062174 · Cited by 142 · see citing works
Self-citationGuo, Y., Chu, X., Parrott, N. J., Brouwer, K. L. R., Hsu, V., Nagar, S., Matsson, P., Sharma, P. K., Snoeys, J., Sugiyama, Y., et al. (2018) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1183 · Cited by 122 · see citing works
Self-citationSaiz‐Rodríguez, M., Almenara, S., Navares‐Gómez, M., Ochoa, D., Román, M. C., Zubiaur, P., Koller, D., Santos, M., Mejía-Abril, G. P., Borobia, A. M., et al. (2020) · Biomedicines · doi:10.3390/biomedicines8040094 · Cited by 118 · see citing works
Parsing interindividual drug variability: an emerging role for systems pharmacology
Turner, R. M., Park, B. K., & Pirmohamed, M. (2015) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1302 · Cited by 91 · see citing works
Badée, J., Achour, B., Rostami‐Hodjegan, A., & Galetin, A. (2015) · Drug Metabolism and Disposition · doi:10.1124/dmd.114.062034 · Cited by 91 · see citing works
Self-citationPharmacogenomics of statins: understanding susceptibility to adverse effects
Kitzmiller, J., Mikulik, E., Dauki, A. M., Mukherjee, C., & Luzum, J. A. (2016) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s86013 · Cited by 92 · see citing works
Genetics, Dyslipidemia, and Cardiovascular Disease: New Insights
Stein, R., Ferrari, F., & Scolari, F. (2019) · Current Cardiology Reports · doi:10.1007/s11886-019-1161-5 · Cited by 83 · see citing works
CYP3A4∗22 Genotyping in Clinical Practice: Ready for Implementation?
Mulder, T. A. M., van Eerden, R. A. G., de With, M., Elens, L., Hesselink, D. A., Matić, M., Bins, S., Mathijssen, R. H. J., & van Schaik, R. H. N. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.711943 · Cited by 82 · see citing works
Bruckmueller, H., & Cascorbi, I. (2021) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2021.1876661 · Cited by 77 · see citing works
Perry, C., Davis, G., Conner, T. M., & Zhang, T. (2020) · Current Pharmacology Reports · doi:10.1007/s40495-020-00212-x · Cited by 75 · see citing works
Tsamandouras, N., Dickinson, G., Guo, Y., Hall, S., Rostami-Hodjegan, A., Galetin, A., & Aarons, L. (2015) · Pharmaceutical Research · doi:10.1007/s11095-014-1581-2 · Cited by 64 · see citing works
Self-citationChoi, H. Y., Bae, K.-S., Cho, S.-H., Ghim, J.-L., Choe, S., Jung, J. A., Jin, S.-J., Kim, H.-S., & Lim, H.-S. (2015) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0000000000000176 · Cited by 49 · see citing works
Elam, M. B., Majumdar, G., Mozhui, K., Gerling, I., VERA, S. R., Fish-Trotter, H. L., Williams, R. W., Childress, R. D., & Raghow, R. (2017) · PLoS ONE · doi:10.1371/journal.pone.0181308 · Cited by 50 · see citing works
Thomas, M., Bayha, C., Vetter, S., Hofmann, U., Schwarz, M., Zanger, U. M., & Braeuning, A. (2015) · Molecular Pharmacology · doi:10.1124/mol.114.097402 · Cited by 39 · see citing works
Wojtyniak, J., Selzer, D., Schwab, M., & Lehr, T. (2021) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.2111 · Cited by 38 · see citing works
Zang, R., Barth, A., Wong, H., Mařı́k, J., Shen, J., Lade, J. M., Grove, K. J., Durk, M. R., Parrott, N. J., Rudewicz, P. J., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00502 · Cited by 37 · see citing works
Takita, H., Barnett, S., Zhang, Y., Ménochet, K., Shen, H., Ogungbenro, K., & Galetin, A. (2020) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12582 · Cited by 36 · see citing works
Self-citationHecht, M., Veigure, R., Couchman, L., S Barker, C. I., Standing, J. F., Takkis, K., Evard, H., Johnston, A., Herodes, K., Leito, I., et al. (2018) · Bioanalysis · doi:10.4155/bio-2018-0078 · Cited by 34 · see citing works
Bakar, N. S., Neely, D., Avery, P. J., Brown, C., Daly, A. K., & Kamali, F. (2017) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.887 · Cited by 32 · see citing works
Luzum, J. A., Theusch, E., Taylor, K. D., Wang, A., Sadée, W., Binkley, P. F., Krauss, R. M., Medina, M. W., & Kitzmiller, J. P. (2015) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000246 · Cited by 32 · see citing works
When the same treatment has different response: The role of pharmacogenomics in statin therapy
Zheng, E., Madura, P., Grandos, J., Broncel, M., Pawlos, A., Woźniak, E., & Gorzelak‐Pabiś, P. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115966 · Cited by 27 · see citing works
Ćetković, Z., Cvijić, S., & Vasiljević, D. (2017) · Drug Development and Industrial Pharmacy · doi:10.1080/03639045.2017.1414835 · Cited by 27 · see citing works
Berinstein, E. M., & Levy, A. P. (2017) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2017.1363887 · Cited by 27 · see citing works
Nies, A., Schaeffeler, E., & Schwab, M. (2022) · Pharmacology and Therapeutics · doi:10.1016/j.pharmthera.2022.108268 · Cited by 21 · see citing works
Tsamandouras, N., Guo, Y., Wendling, T., Hall, S. D., Galetin, A., & Aarons, L. J. (2016) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0000000000000252 · Cited by 22 · see citing works
Self-citationPrieto Garcia, L., Lundahl, A., Ahlström, C., Vildhede, A., Lennernäs, H., & Sjögren, E. (2022) · CPT: Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12837 · Cited by 21 · see citing works
Rostami‐Hodjegan, A., Al‐Majdoub, Z. M., von Grabowiecki, Y., Yee, K. L., Sahoo, S., Breitwieser, W., Galetin, A., Gibson, C. R., & Achour, B. (2024) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3291 · Cited by 20 · see citing works
Self-citationMauriello, A., Ascrizzi, A., Molinari, R., Falco, L., Caturano, A., D’Andrea, A., & Russo, V. (2023) · Genes · doi:10.3390/genes14112057 · Cited by 18 · see citing works
Mitsis, A., Khattab, E., Kyriakou, M., Sokratous, S., Sakellaropoulos, S., Tzikas, S., Kadoglou, N. P. E., & Kassimis, G. (2025) · Biomedicines · doi:10.3390/biomedicines13071723 · Cited by 16 · see citing works
Lyauk, Y. K., Stage, C., Bergmann, T. K., Ferrero‐Miliani, L., Bjerre, D., Thomsen, R., Dalhoff, K., Rasmussen, H., & Jűrgens, G. (2016) · Clinical and Translational Science · doi:10.1111/cts.12423 · Cited by 15 · see citing works
Chronopharmacology of simvastatin on hyperlipidaemia in high‐fat diet‐fed obese mice
Li, H., Rabearivony, A., Zhang, W., Chen, S., An, X., & Liu, C. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15709 · Cited by 14 · see citing works
Kim, J. S., Shim, S.-Y., Yee, J., Choi, K. H., & Gwak, H. S. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1201083 · Cited by 13 · see citing works
ZNF542P is a pseudogene associated with LDL response to simvastatin treatment
Kim, K., Theusch, E., Kuang, Y., Dosé, A. C., Mitchel, K., Cubitt, C. C., Chen, Y. I., Krauss, R. M., & Medina, M. W. (2018) · Scientific Reports · doi:10.1038/s41598-018-30859-y · Cited by 12 · see citing works
Dietary supplements, cytochrome metabolism, and pharmacogenetic considerations
Matura, J. M., Shea, L. A., & Bankes, V. A. (2021) · Irish Journal of Medical Science (1971 -) · doi:10.1007/s11845-021-02828-4 · Cited by 12 · see citing works
Ujihira, Y., Tan, S. P. F., Scotcher, D., & Galetin, A. (2025) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.70008 · Cited by 10 · see citing works
Self-citationWillis, B. A., Andersen, S. W., Ayan‐Oshodi, M., James, D. E., Liffick, E., Hillgren, K. M., Guo, Y., & Monk, S. A. (2019) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.1500 · Cited by 10 · see citing works
Self-citationPharmacogenetics in Cardiovascular Medicine
Weeke, P. E. (2018) · Advances in pharmacology · doi:10.1016/bs.apha.2018.04.002 · Cited by 10 · see citing works
A population pharmacokinetic model for simvastatin and its metabolites in children and adolescents
Ogungbenro, K., Wagner, J. B., Abdel‐Rahman, S. M., Leeder, J. S., & Galetin, A. (2019) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-019-02697-y · Cited by 8 · see citing works
Self-citationArruda, M. B., Campagnari, F., de Almeida, T. B., Couto-Fernandez, J. C., Tanuri, A., & Cardoso, C. C. (2016) · PLoS ONE · doi:10.1371/journal.pone.0163170 · Cited by 8 · see citing works
Hoosain, N., Pearce, B., Jacobs, C., & Benjeddou, M. (2016) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2016.0115 · Cited by 6 · see citing works
Galetin, A., Zhang, L., Rodrigues, A. D., & Huang, S. M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819869-8.00013-6 · Cited by 6 · see citing works
Self-citationTipnoppanon, S., Udomnilobol, U., Siwamogsatham, S., Vorasettakarnkij, Y., Sukasem, C., Prueksaritanont, T., Chariyavilaskul, P., Yodsurang, V., Srimatimanon, T., Chamnanphon, M., et al. (2025) · Clinical and Translational Science · doi:10.1111/cts.70225 · Cited by 5 · see citing works
Pohlen, M., Zdovc, J. A., Trontelj, J., Mravljak, J., Matjaž, M. G., Grabnar, I., Snoj, T., & Dreu, R. (2021) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2021.12.004 · Cited by 5 · see citing works
Hoste, E., Paquot, A., Panin, N., Horion, S., Hamdaoui, H. E., Muccioli, G. G., Haufroid, V., & Elens, L. (2022) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0000000000001043 · Cited by 5 · see citing works
New Drug Development and Clinical Trial Design by Applying Genomic Information Management
Ko, Y. K., & Gim, J. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14081539 · Cited by 5 · see citing works
El‐Khateeb, E., Chinnadurai, R., Al-Qassabi, J., Scotcher, D., Darwich, A. S., Kalra, P. A., & Rostami‐Hodjegan, A. (2023) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0000000000001108 · Cited by 4 · see citing works
Self-citationRajput, M., Rizvi, S., Pratap, P. D., Raza, S. T., Siddiqi, Z., & Khare, V. (2025) · Egyptian Journal of Medical Human Genetics · doi:10.1186/s43042-025-00787-4 · Cited by 3 · see citing works
Divsalar, B., Kalantari, T., Mohebbi, S., Bahmanimehr, A., Dehbidi, G. R., & Borhani‐Haghighi, A. (2021) · Meta Gene · doi:10.1016/j.mgene.2021.100932 · Cited by 3 · see citing works
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Shatnawi, A. A., Kamran, Z., & Al–Share, Q. Y. (2022) · Personalized Medicine · doi:10.2217/pme-2022-0041 · Cited by 3 · see citing works
Botton, M. R., Bandinelli, E., Leiria, T. L. L., Rohde, L. E. P., & Hutz, M. H. (2014) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0000000000000109 · Cited by 3 · see citing works
Mokbel, K., Weedon, M. N., DANIELS, R., Moye, V., & Jackson, L. M. (2025) · British Journal of General Practice · doi:10.3399/bjgp.2024.0806 · Cited by 2 · see citing works
Mauriello, A., Falco, A. D., Correra, A., D’Andrea, A., Giallauria, F., Giordano, A., & Russo, V. (2026) · Current Atherosclerosis Reports · doi:10.1007/s11883-026-01414-2 · Cited by 2 · see citing works
Costa, A., Medeiros, J. I. M., Kang, W.-H., Yamamoto, P. A., de Gaitani, C. M., Vasconcelos, M. E. D., da Silva, R. M., Kemp, R., Sankarankutty, A. K., Salgado, W., et al. (2024) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.6110 · Cited by 2 · see citing works
Han, Y., Bian, Z., Gu, H., Guo, D., Li, R., Liu, L., Wang, D., & Peng, Y. (2026) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2026.111873 · Cited by 1 · see citing works
Lusiki, Z., Blom, D. J., Soko, N. D., Malema, S., Jones, E. S. W., Rayner, B. L., Blackburn, J. M., Sinxadi, P., Dandara, M. T. L., & Dandara, C. (2023) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2023.0122 · Cited by 1 · see citing works
Leong, C. W., Yee, K. M., Rani, T. A., Lau, K. J., Ahmad, S., Amran, A., Hassan, F. W. M., & Kumar, N. (2024) · Clinical Pharmacology in Drug Development · doi:10.1002/cpdd.1411 · Cited by 1 · see citing works
Kandel, B. A. (2014) · OPUS Publication Server of the University of Stuttgart (University of Stuttgart) · doi:10.18419/opus-8263
Bartsch, F., Grzegorzewski, J., Pujol, H. L., Tautenhahn, H., & König, M. (2023) · medRxiv · doi:10.1101/2023.02.01.23285358
The Construction of CRISPR-Cas9 System Targeting Vector for CYP3A4 Gene in Hepatic Cell Lines
Hatta, F. H. M., Aziz, F. N. A., Shafiq‐ur‐Rehman, & Othman, A. A. (2024) · Journal of Advanced Research in Applied Sciences and Engineering Technology · doi:10.37934/araset.43.2.178188
Morse, B. L., Han, B., Alberts, J. J., Posada, M. M., Dickinson, G. L., & Hall, S. D. (2026) · The AAPS Journal · doi:10.1208/s12248-026-01299-8
Self-citation
- Authors
- Tsamandouras, N., Dickinson, G., Guo, Y., Hall, S., Rostami-Hodjegan, A., Galetin, A., & Aarons, L.
- Affiliations
- University of Manchester (GB)
- Eli Lilly (United States) (US)
- Corresponding author
- Aarons, L
- Venue
- Clinical Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2014-03-05
- Volume
- 96
- Issue
- 1
- Pages
- 90-100
- ISSN
- 0009-9236 (ISSN-L)
- 1532-6535
- OpenAlex
- W2142436506
- Cited by
- 68
- References
- 41
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 6 · 2020: 6 · 2019: 5 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 6 · 2014: 4
- FWCI
- 7.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- simvastatin, simvastatin acid, pharmacokinetics, genetic polymorphism, population pharmacokinetic model, SLCO1B1, CYP3A5, SLCO2B1, ABCG2, PPARα, CYP3A4, myopathy, covariate effects, Japanese ethnicity
- MeSH terms
- Genotype, Humans, Models, Biological, Polymorphism, Genetic, Risk Factors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin, White People, Asian People
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