Skip to main content
SpringerLink
Log in

Impact of Menopause on Pharmacokinetics of Rosuvastatin Compared with Premenopausal Women

  • Original Paper
  • Published:
European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Abstract

Background and Objective

Rosuvastatin is used to treat dyslipidemia and its use is quite frequent among postmenopausal women. Menopause significantly affects the pharmacokinetics of drugs, and altered drug response and therapeutic efficacy may be anticipated in postmenopausal women compared with premenopausal women. The current study is based on assessment of differences in pharmacokinetics of rosuvastatin between pre- and postmenopausal women of Asian ethnicity.

Methods

Volunteers were administered a single oral dose of rosuvastatin 40 mg in an open-label and non-controlled pharmacokinetic study. A reversed-phase HPLC method was applied for quantification of rosuvastatin in plasma samples. Student’s t test was used to compare the pharmacokinetic parameters of rosuvastatin between pre- and postmenopausal women at the 95 % confidence interval.

Results

The C max (premenopausal = 58.2 ± 29.1, postmenopausal = 12.2 ± 3.1 ng/ml), \([{\text{AUC}} ]_{0}^{8}\) (premenopausal = 272.6 ± 107.3 ng·h/ml, postmenopausal = 58.8 ± 16.6 ng·h/ml), and \([{\text{AUC}} ]_{0}^{\infty }\) (premenopausal = 366.1 ± 169, postmenopausal = 66.4 ± 12.9 ng·h/ml) of rosuvastatin were significantly higher (p < 0.05) in premenopausal compared with postmenopausal women. The Vd/F of rosuvastatin was significantly higher (p < 0.05) in postmenopausal women compared with women, and CL/F was also significantly (p < 0.05) faster in postmenopausal women when compared at the 95 % confidence interval.

Conclusion

Rosuvastatin plasma level was significantly higher in premenopausal compared with postmenopausal women, which raises the question whether the latter are getting due therapeutic results, as after the menopause women experience more frequent cardiovascular problems and dyslipidemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Martin PD, Warwick MJ, Dane AL, Hill SJ, Giles PB, Phillips PJ, et al. Metabolism, excretion, and pharmacokinetics of rosuvastatin in healthy adult male volunteers. Clin Ther. 2003;25(11):2822–35.

    Article  CAS  PubMed  Google Scholar 

  2. Bellosta S, Paoletti R, Corsini A. Safety of statins focus on clinical pharmacokinetics and drug interactions. Circulation. 2004;109(23 Suppl 1):III-50–III-57.

  3. Niemi M, Pasanen MK, Neuvonen PJ. SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not fluvastatin. Clin Pharmacol Ther. 2006;80(4):356–66.

    Article  CAS  PubMed  Google Scholar 

  4. Matthews KA, Meilahn E, Kuller LH, Kelsey SF, Caggiula AW, Wing RR. Menopause and risk factors for coronary heart disease. N Engl J Med. 1989;321(10):641–6.

    Article  CAS  PubMed  Google Scholar 

  5. Feng Y, Hong X, Wilker E, Li Z, Zhang W, Jin D, et al. Effects of age at menarche, reproductive years, and menopause on metabolic risk factors for cardiovascular diseases. Atherosclerosis. 2008;196(2):590–7.

    Article  CAS  PubMed  Google Scholar 

  6. Carr MC. The emergence of the metabolic syndrome with menopause. J Clin Endocrinol Metab. 2003;88(6):2404–11.

    Article  CAS  PubMed  Google Scholar 

  7. Pasanen M, Fredrikson H, Neuvonen P, Niemi M. Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. Clin Pharmacol Ther. 2007;82(6):726–33.

    Article  CAS  PubMed  Google Scholar 

  8. Zhang W, Yu B-N, He Y-J, Fan L, Li Q, Liu Z-Q, et al. Role of BCRP 421C>—a polymorphism on rosuvastatin pharmacokinetics in healthy Chinese males. Clin Chim Acta. 2006;373(1):99–103.

    Article  CAS  PubMed  Google Scholar 

  9. Keskitalo J, Zolk O, Fromm M, Kurkinen K, Neuvonen P, Niemi M. ABCG2 polymorphism markedly affects the pharmacokinetics of atorvastatin and rosuvastatin. Clin Pharmacol Ther. 2009;86(2):197–203.

    Article  CAS  PubMed  Google Scholar 

  10. Choi J, Lee M, Cho J, Lee J, Kim K, Park K. Influence of OATP1B1 genotype on the pharmacokinetics of rosuvastatin in Koreans. Clin Pharmacol Ther. 2007;83(2):251–7.

    Article  PubMed  Google Scholar 

  11. Martin PD, Dane AL, Nwose OM, Schneck DW, Warwick MJ. No effect of age or gender on the pharmacokinetics of rosuvastatin: a new HMG-CoA reductase inhibitor. J Clin Pharmacol. 2002;42(10):1116–21.

    Article  CAS  PubMed  Google Scholar 

  12. Shah Y, Iqbal Z, Ahmad L, Khan A, Khan MI, Nazir S, et al. Simultaneous determination of rosuvastatin and atorvastatin in human serum using RP-HPLC/UV detection: method development, validation and optimization of various experimental parameters. J Chromatogr B. 2011;879(9):557–63.

    Article  CAS  Google Scholar 

  13. Carr MC. The emergence of the metabolic syndrome with menopause. J Clin Endocrinol Metab. 2003;88(6):2404–11.

    Article  CAS  PubMed  Google Scholar 

  14. Laurell CB, Rannevik G. A comparison of plasma protein changes induced by danazol, pregnancy, and estrogens. J Clin Endocrinol Metab. 1979;49(5):719–25.

    Article  Google Scholar 

  15. Trauner M, Arrese M, Soroka C, Ananthanarayanan M, Koeppel T, Schlosser S, et al. The rat canalicular conjugate export pump (Mrp2) is down-regulated in intrahepatic and obstructive cholestasis. Gastroenterology. 1997;113(1):255–64.

    Article  CAS  PubMed  Google Scholar 

  16. Wang H, Zhou L, Gupta A, Vethanayagam RR, Zhang Y, Unadkat JD, et al. Regulation of BCRP/ABCG2 expression by progesterone and 17β-estradiol in human placental BeWo cells. Am J Physiol Endocrinol Metab. 2006;290(5):E798–807.

    Article  CAS  PubMed  Google Scholar 

  17. To KK, Hu M, Tomlinson B. Expression and activity of ABCG2, but not ABCB1 or OATP1B1, are associated with cholesterol levels: evidence from in vitro and in vivo experiments. Pharmacogenomics. 2014;15(8):1091–104.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We pay special thanks to the University of Peshawar for providing facilities and technical support to conduct the study. We are grateful to Ferozsons Limited for providing us with standards of rosuvastatin.

Conflict of interest

No conflict of interest exists.

Author information

Authors and Affiliations

  1. Department of Pharmacy, Kohat university of Science and Technology, Kohat, Pakistan

    Shabnam Nazir

  2. Department of Pharmacy, University of Peshawar, Peshawar, KPK, Pakistan

    Zafar Iqbal & Fazli Nasir

Authors
  1. Shabnam Nazir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zafar Iqbal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fazli Nasir
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zafar Iqbal.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nazir, S., Iqbal, Z. & Nasir, F. Impact of Menopause on Pharmacokinetics of Rosuvastatin Compared with Premenopausal Women. Eur J Drug Metab Pharmacokinet 41, 505–509 (2016). https://doi.org/10.1007/s13318-015-0285-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13318-015-0285-2

Keywords

Search

Navigation