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UGT1A1*28 is Associated with Decreased Systemic Exposure of Atorvastatin Lactone

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Abstract

Background

Atorvastatin is commonly used to reduce cholesterol. Atorvastatin acid is converted to its corresponding lactone form spontaneously or via glucuronidation mediated by uridine diphosphate glucuronosyltransferase (UGT) 1A1 and 1A3. Atorvastatin lactone is pharmacologically inactive, but is suspected to be muscle toxic and cause statin-induced myopathy (SIM). A several fold increase in systemic exposure of atorvastatin lactone has previously been observed in patients with SIM compared with healthy control subjects. In this study we aimed to investigate the association between polymorphisms in the UGT1A gene locus and plasma atorvastatin lactone levels.

Methods

DNA was extracted from whole blood obtained from a previous pharmacokinetic study of patients carefully diagnosed as having true SIM (n = 13) and healthy control subjects (n = 15). The UGT1A1*28(TA) 7 , UGT1A3*2, UGT1A3*3, and UGT1A3*6 polymorphisms were detected by pyrosequencing.

Results

Carriers of the low-expression allele UGT1A1*28(TA) 7 tended to have lower levels of atorvastatin lactone (p < 0.05) than carriers with the normal-activity allele (TA) 6 .

Conclusion

The low-expression UGT1A1*28(TA) 7 allele seems to be associated with decreased systemic exposure of the suspected muscle-toxic metabolite atorvastatin lactone.

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Acknowledgments

This work was funded by the Division of Diagnostics and Intervention, Oslo University Hospital, Norway and South-Eastern Norway Regional Health Authority. The authors have no conflict of interest that are relevant to the content of this article.

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Authors and Affiliations

  1. Department of Medical Biochemistry, Oslo University Hospital, University of Oslo, Nydalen, P.O. Box 4956, 0424, Oslo, Norway

    Camilla Stormo

  2. Helse Møre and Romsdal Health Trust, Department of Internal Medicine Ålesund and University of Oslo, Ålesund Hospital, Åsehaugenh 5, 6017, Ålesund, Norway

    Martin P. Bogsrud

  3. Lipid Clinic, Oslo University Hospital, Rikshospitalet, Nydalen, P.O. Box 4950, 0424, Oslo, Norway

    Martin P. Bogsrud & Kjetil Retterstøl

  4. School of Pharmacy, University of Oslo, Oslo, Norway

    Monica Hermann & Anders Åsberg

  5. Fürst Medical Laboratory, Oslo, Norway

    Armin P. Piehler

  6. Department of Pharmacology, Oslo University Hospital, Ullevål, Nydalen, P.O. Box 4956, 0424, Oslo, Norway

    Marianne K. Kringen

Authors
  1. Camilla Stormo
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  2. Martin P. Bogsrud
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  3. Monica Hermann
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  4. Anders Åsberg
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  5. Armin P. Piehler
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  6. Kjetil Retterstøl
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  7. Marianne K. Kringen
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Corresponding author

Correspondence to Camilla Stormo.

Additional information

C. Stormo and M. P. Bogsrud contributed equally to the manuscript.

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Stormo, C., Bogsrud, M.P., Hermann, M. et al. UGT1A1*28 is Associated with Decreased Systemic Exposure of Atorvastatin Lactone. Mol Diagn Ther 17, 233–237 (2013). https://doi.org/10.1007/s40291-013-0031-x

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  • DOI: https://doi.org/10.1007/s40291-013-0031-x

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