Skip to main content
SpringerLink
Log in

Maternal Ezetimibe Concentrations Measured in Breast Milk and Its Use in Breastfeeding Infant Exposure Predictions

  • Original Research Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Abstract

Background

Lactating mothers taking ezetimibe, an antihyperlipidemic agent, may be hesitant to breastfeed despite the known benefit of breastfeeding to both mother and infant. Currently, no data exist on the presence or concentration of ezetimibe and its main active metabolite, ezetimibe-glucuronide (EZE-glucuronide), in human breast milk.

Methods

Voluntary breast milk samples containing ezetimibe and EZE-glucuronide were attained from lactating mothers taking ezetimibe as part of their treatment. An assay was developed and validated to measure ezetimibe and EZE-glucuronide concentrations in breast milk. A workflow that utilized a developed and evaluated pediatric physiologically based pharmacokinetic (PBPK) model, the measured concentrations in milk, and weight-normalized breast milk intake volumes was applied to predict infant exposures and determine the upper area under the curve ratio (UAR).

Results

Fifteen breast milk samples from two maternal-infant pairs were collected. The developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay showed an analytical range of 0.039–5.0 ng/mL and 0.39–50.0 ng/mL for ezetimibe and EZE-glucuronide, respectively. The measured concentrations in the breast milk samples were 0.17–1.02 ng/mL and 0.42–2.65 ng/mL of ezetimibe and EZE-glucuronide, respectively. The evaluated pediatric PBPK model demonstrated minimal exposure overlap in adult therapeutic dose and breastfed infant simulated area under the concentration-time curve from time zero to 24 h (AUC24). Calculated UAR across infant age groups ranged from 0.0015 to 0.0026.

Conclusions

PBPK model-predicted ezetimibe and EZE-glucuronide exposures and UAR suggest that breastfeeding infants would receive non-therapeutic exposures. Future work should involve a ‘mother-infant pair study’ to ascertain breastfed infant plasma ezetimibe and EZE-glucuronide concentrations to confirm the findings of this work.

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
Fig. 4

Similar content being viewed by others

References

  1. Godfrey JR, Lawrence RA. Toward optimal health: the maternal benefits of breastfeeding. J Women’s Health (2002). 2010;19(9):1597–602.

    Article  Google Scholar 

  2. Chowdhury R, Sinha B, Sankar MJ, Taneja S, Bhandari N, Rollins N, et al. Breastfeeding and maternal health outcomes: a systematic review and meta-analysis. Acta Paediatr. 2015;104(467):96–113.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ip S, Chung M, Raman G, Chew P, Magula N, DeVine D, et al. Breastfeeding and maternal and infant health outcomes in developed countries. Evid Rep Technol Assess. 2007;153:1–186.

    Google Scholar 

  4. Ip S, Chung M, Raman G, Trikalinos TA, Lau J. A summary of the Agency for Healthcare Research and Quality’s evidence report on breastfeeding in developed countries. Breastfeed Med. 2009;4(Suppl 1):S17-30.

    Article  PubMed  Google Scholar 

  5. Chantry CJ, Howard CR, Auinger P. Full breastfeeding duration and associated decrease in respiratory tract infection in US children. Pediatrics. 2006;117(2):425–32.

    Article  PubMed  Google Scholar 

  6. Greer FR, Sicherer SH, Burks AW. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics. 2008;121(1):183–91.

    Article  PubMed  Google Scholar 

  7. Mazer-Amirshahi M, Samiee-Zafarghandy S, Gray G, van den Anker JN. Trends in pregnancy labeling and data quality for US-approved pharmaceuticals. Am J Obstet Gynecol. 2014;211(6):690.e1-11.

    Article  PubMed  Google Scholar 

  8. Jones H, Rowland-Yeo K. Basic concepts in physiologically based pharmacokinetic modeling in drug discovery and development. CPT Pharmacomet Syst Pharmacol. 2013;2(8): e63.

    Article  Google Scholar 

  9. Yeung CHT, Ito S, Autmizguine J, Edginton AN. Incorporating breastfeeding-related variability with physiologically based pharmacokinetic modeling to predict infant exposure to maternal medication through breast milk: A workflow applied to lamotrigine. AAPS J. 2021;23(4):70.

    Article  CAS  PubMed  Google Scholar 

  10. Yeung CHT, Fong S, Malik PRV, Edginton AN. Quantifying breast milk intake by term and preterm infants for input into paediatric physiologically based pharmacokinetic models. Matern Child Nutr. 2020;16(2): e12938.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bennett PN, Notrianni LJ. Risk from drugs in breast milk: an analysis by relative dose. Br J Clin Pharmacol. 1996;42:623–4.

    Google Scholar 

  12. National Institutes of Health Clinical Center (CC). Higher-Dose Ezetimibe to Treat Homozygous Sitosterolemia. 2008 [cited 6 Feb 2023]. https://clinicaltrials.gov/ct2/show/NCT00099996.

  13. European Medicines Agency. Ezetimibe tablet 10 mg product-specific bioequivalence guidance. European Medicines Agency; 2018.

    Google Scholar 

  14. Kosoglou T, Maxwell S, Chung C, Batra V, Statkevich P. Dose-proportionality of ezetimibe. Clin Pharmacol Ther. 2002;71(2):P97.

    Google Scholar 

  15. Pharmacutical and Food Safety Bureau. Report on the Deliberation Results-Zetia Tablets 10 mg. Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour, and Welfare; 2007.

    Google Scholar 

  16. Schering-Plough. Review Report-Zetia Tablets 10 mg. Pharmaceutical and Medical Devices Agency; 2003.

    Google Scholar 

  17. Van Heek M, France CF, Compton DS, McLeod RL, Yumibe NP, Alton KB, et al. In vivo metabolism-based discovery of a potent cholesterol absorption inhibitor, SCH58235, in the rat and rhesus monkey through the identification of the active metabolites of SCH48461. J Pharmacol Exp Ther. 1997;283(1):157–63.

    PubMed  Google Scholar 

  18. Patrick JE, Kosoglou T, Stauber KL, Alton KB, Maxwell SE, Zhu Y, et al. Disposition of the selective cholesterol absorption inhibitor ezetimibe in healthy male subjects. Drug Metab Dispos. 2002;30(4):430–7.

    Article  CAS  PubMed  Google Scholar 

  19. Oswald S, Haenisch S, Fricke C, Sudhop T, Remmler C, Giessmann T, et al. Intestinal expression of P-glycoprotein (ABCB1), multidrug resistance associated protein 2 (ABCC2), and uridine diphosphate-glucuronosyltransferase 1A1 predicts the disposition and modulates the effects of the cholesterol absorption inhibitor ezetimibe in humans. Clin Pharmacol Ther. 2006;79(3):206–17.

    Article  CAS  PubMed  Google Scholar 

  20. Oswald S, König J, Lütjohann D, Giessmann T, Kroemer HK, Rimmbach C, et al. Disposition of ezetimibe is influenced by polymorphisms of the hepatic uptake carrier OATP1B1. Pharmacogenet Genomics. 2008;18(7):559–68.

    Article  CAS  PubMed  Google Scholar 

  21. de Waart DR, Vlaming ML, Kunne C, Schinkel AH, Oude Elferink RP. Complex pharmacokinetic behavior of ezetimibe depends on abcc2, abcc3, and abcg2. Drug Metab Dispos Biol Fate Chem. 2009;37(8):1698–702.

    Article  PubMed  Google Scholar 

  22. MSP Singapore Co. Clinical pharmacology and biopharmaceutics review(s)—ZETIA. Center for Drug Evaluation and Research; 2001.

    Google Scholar 

  23. Sanis Health Inc. Ezetimibe Tablets Package Insert Product Monograph. Sanis Health Inc.; 2014.

    Google Scholar 

  24. Drugs and Lactation Database (LactMed®): Ezetimibe. 19 Oct 2020.

  25. Guo L, Wang MM, He M, Qiu FR, Jiang J. Simultaneous determination of ezetimibe and its glucuronide metabolite in human plasma by solid phase extraction and liquid chromatography-tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci. 2015;986–987:108–14.

    Article  Google Scholar 

  26. Broughton PM. Carry-over in automatic analysers. J Autom Chem. 1984;6(2):94–5.

    Article  CAS  Google Scholar 

  27. Maharaj AR, Barrett JS, Edginton AN. A workflow example of PBPK modeling to support pediatric research and development: case study with lorazepam. AAPS J. 2013;15(2):455–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Rodgers T, Leahy D, Rowland M. Physiologically based pharmacokinetic modeling 1: predicting the tissue distribution of moderate-to-strong bases. J Pharm Sci. 2005;94(6):1259–76.

    Article  CAS  PubMed  Google Scholar 

  29. Rodgers T, Rowland M. Physiologically based pharmacokinetic modelling 2: predicting the tissue distribution of acids, very weak bases, neutrals and zwitterions. J Pharm Sci. 2006;95(6):1238–57.

    Article  CAS  PubMed  Google Scholar 

  30. Rodgers T, Rowland M. Mechanistic approaches to volume of distribution predictions: understanding the processes. Pharm Res. 2007;24(5):918–33.

    Article  CAS  PubMed  Google Scholar 

  31. Schmitt W. General approach for the calculation of tissue to plasma partition coefficients. Toxicol In Vitro. 2008;22(2):457–67.

    Article  CAS  PubMed  Google Scholar 

  32. Ghosal A, Hapangama N, Yuan Y, Achanfuo-Yeboah J, Iannucci R, Chowdhury S, et al. Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetia). Drug Metab Dispos. 2004;32(3):314–20.

    Article  CAS  PubMed  Google Scholar 

  33. Shiran MR, Proctor NJ, Howgate EM, Rowland-Yeo K, Tucker GT, Rostami-Hodjegan A. Prediction of metabolic drug clearance in humans: in vitro-in vivo extrapolation vs allometric scaling. Xenobiotica. 2006;36(7):567–80.

    Article  CAS  PubMed  Google Scholar 

  34. Rostami-Hodjegan A, Tucker GT. Simulation and prediction of in vivo drug metabolism in human populations from in vitro data. Nat Rev Drug Discov. 2007;6(2):140–8.

    Article  CAS  PubMed  Google Scholar 

  35. Nishimura M, Naito S. Tissue-specific mRNA expression profiles of human ATP-binding cassette and solute carrier transporter superfamilies. Drug Metab Pharmacokinet. 2005;20(6):452–77.

    Article  CAS  PubMed  Google Scholar 

  36. Nishimura M, Naito S. Tissue-specific mRNA expression profiles of human phase I metabolizing enzymes except for cytochrome P450 and phase II metabolizing enzymes. Drug Metab Pharmacokinet. 2006;21(5):357–74.

    Article  CAS  PubMed  Google Scholar 

  37. Nishimura M, Yaguti H, Yoshitsugu H, Naito S, Satoh T. Tissue distribution of mRNA expression of human cytochrome P450 isoforms assessed by high-sensitivity real-time reverse transcription PCR. Yakugaku Zasshi. 2003;123(5):369–75.

    Article  CAS  PubMed  Google Scholar 

  38. Achour B, Dantonio A, Niosi M, Novak JJ, Fallon JK, Barber J, et al. Quantitative characterization of major hepatic UDP-glucuronosyltransferase enzymes in human liver microsomes: comparison of two proteomic methods and correlation with catalytic activity. Drug Metab Dispos. 2017;45(10):1102–12.

    Article  CAS  PubMed  Google Scholar 

  39. Prasad B, Johnson K, Billington S, Lee C, Chung GW, Brown CD, et al. Abundance of drug transporters in the human kidney cortex as quantified by quantitative targeted proteomics. Drug Metab Dispos. 2016;44(12):1920–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Food and Drug Administration. Guidance for industry—dissolution testing of immediate release solid oral dosage forms. Center for Drug Evaluation and Research; 1997.

    Google Scholar 

  41. Burt HJ, Riedmaier AE, Harwood MD, Crewe HK, Gill KL, Neuhoff S. Abundance of hepatic transporters in caucasians: a meta-analysis. Drug Metab Dispos. 2016;44(10):1550–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Willmann S, Höhn K, Edginton A, Sevestre M, Solodenko J, Weiss W, et al. Development of a physiology-based whole-body population model for assessing the influence of individual variability on the pharmacokinetics of drugs. J Pharmacokinet Pharmacodyn. 2007;34(3):401–31.

    Article  PubMed  Google Scholar 

  43. Edginton AN, Schmitt W, Willmann S. Development and evaluation of a generic physiologically based pharmacokinetic model for children. Clin Pharmacokinet. 2006;45(10):1013–34.

    Article  CAS  PubMed  Google Scholar 

  44. Edginton AN, Schmitt W, Voith B, Willmann S. A mechanistic approach for the scaling of clearance in children. Clin Pharmacokinet. 2006;45(7):683–704.

    Article  CAS  PubMed  Google Scholar 

  45. Divakaran K, Hines RN, McCarver DG. Human hepatic UGT2B15 developmental expression. Toxicol Sci. 2014;141(1):292–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Badée J, Qiu N, Collier AC, Takahashi RH, Forrest WF, Parrott N, et al. Characterization of the ontogeny of hepatic UDP-glucuronosyltransferase enzymes based on glucuronidation activity measured in human liver microsomes. J Clin Pharmacol. 2019;59(Suppl 1):S42–55.

    PubMed  Google Scholar 

  47. Prasad B, Gaedigk A, Vrana M, Gaedigk R, Leeder JS, Salphati L, et al. Ontogeny of hepatic drug transporters as quantified by LC-MS/MS proteomics. Clin Pharmacol Ther. 2016;100(4):362–70.

    Article  CAS  PubMed  Google Scholar 

  48. Kusters DM, Caceres M, Coll M, Cuffie C, Gagné C, Jacobson MS, et al. Efficacy and safety of ezetimibe monotherapy in children with heterozygous familial or nonfamilial hypercholesterolemia. J Pediatrics. 2015;166(6):1377-84.e1-3.

    Article  CAS  Google Scholar 

  49. Burt VL, Harris T. The third National Health and Nutrition Examination Survey: contributing data on aging and health. Gerontologist. 1994;34(4):486–90.

    Article  CAS  PubMed  Google Scholar 

  50. Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey: NHANES III. [cited 17 Jan 2023]. Available at: https://wwwn.cdc.gov/nchs/nhanes/nhanes3/default.aspx

  51. Yeung CHT, Houle SKD, Anderson PO, Best BM, Dubinsky S, Edginton AN. Addressing maternal medication use during breastfeeding using clinical resources and a novel physiologically based pharmacokinetic model-derived metric: A qualitative study. Front Pediatr. 2023;11:1147566.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Saito J, Kaneko K, Abe S, Yakuwa N, Kawasaki H, Suzuki T, et al. Pravastatin concentrations in maternal serum, umbilical cord serum, breast milk and neonatal serum during pregnancy and lactation: A case study. J Clin Pharm Ther. 2022;47(5):703–6.

    Article  CAS  PubMed  Google Scholar 

  53. Yang H, Zhang D, Mei S, Zhao Z. Simultaneous determination of plasma lamotrigine, lamotrigine N2-glucuronide and lamotrigine N2-oxide by UHPLC-MS/MS in epileptic patients. J Pharm Biomed Anal. 2022;220: 115017.

    Article  CAS  PubMed  Google Scholar 

  54. Cooper JD, Shearsby NJ, Taylor JE, Fook Sheung CT. Simultaneous determination of lamotrigine and its glucuronide and methylated metabolites in human plasma by automated sequential trace enrichment of dialysates and gradient high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl. 1997;702(1–2):227–33.

    Article  CAS  PubMed  Google Scholar 

  55. Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB. Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467–94.

    Article  CAS  PubMed  Google Scholar 

  56. Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). Clinical lactation studies: considerations for study design. Rockville: US Department of Health and Human Services, Food and Drug Administration; 2019.

    Google Scholar 

  57. Reyderman L, Kosoglou T, Statkevich L, Pemper L, Maxwell S, Batra V. Pharmacokinetics of ezetimibe in subjects with normal renal function or severe chronic renal insufficiency. Clin Pharmacol Ther. 2002;71(2):P27.

    Google Scholar 

  58. US FDA. Guidance for industry—dissolution testing of immediate release solid oral dosage forms. Center for Drug Evaluation and Research; 1997.

    Google Scholar 

  59. Bae J-W, Choi C-I, Park S-H, Jang C-G, Lee S-Y. Analytical LC-MS/MS method for ezetimibe and its application for pharmacokinetic study. J Liq Chromatogr Relat Technol. 2012;35(1):141–52.

    Article  CAS  Google Scholar 

  60. Bergman AJ, Burke J, Larson P, Johnson-Levonas AO, Reyderman L, Statkevich P, et al. Interaction of single-dose ezetimibe and steady-state cyclosporine in renal transplant patients. J Clin Pharmacol. 2006;46(3):328–36.

    Article  CAS  PubMed  Google Scholar 

  61. Gustavson LE, Schweitzer SM, Burt DA, Achari R, Rieser MJ, Edeki T, et al. Evaluation of the potential for pharmacokinetic interaction between fenofibrate and ezetimibe: a phase I, open-label, multiple-dose, three-period crossover study in healthy subjects. Clin Ther. 2006;28(3):373–87.

    Article  CAS  PubMed  Google Scholar 

  62. Jackson A, D’Avolio A, Watson V, Bonora S, Back D, Taylor J, et al. Pharmacokinetics and safety of the co-administration of the antiretroviral raltegravir and the lipid-lowering drug ezetimibe in healthy volunteers. J Antimicrob Chemother. 2011;66(4):885–9.

    Article  CAS  PubMed  Google Scholar 

  63. Kim CH, An H, Kim SH, Shin D. Pharmacokinetic and pharmacodynamic interaction between ezetimibe and rosuvastatin in healthy male subjects. Drug Des Dev Ther. 2017;11:3461–9.

    Article  CAS  Google Scholar 

  64. Kim H, Choi HY, Kim YH, Bae KS, Jung J, Son H, et al. Pharmacokinetic interactions and tolerability of rosuvastatin and ezetimibe: an open-label, randomized, multiple-dose, crossover study in healthy male volunteers. Drug Des Dev Ther. 2018;12:815–21.

    Article  CAS  Google Scholar 

  65. Kosoglou T, Statkevich P, Fruchart JC, Pember LJ, Reyderman L, Cutler DL, et al. Pharmacodynamic and pharmacokinetic interaction between fenofibrate and ezetimibe. Curr Med Res Opin. 2004;20(8):1197–207.

    Article  CAS  PubMed  Google Scholar 

  66. Kosoglou T, Statkevich P, Yang B, Suresh R, Zhu Y, Boutros T, et al. Pharmacodynamic interaction between ezetimibe and rosuvastatin. Curr Med Res Opin. 2004;20(8):1185–95.

    Article  CAS  PubMed  Google Scholar 

  67. Oswald S, Meyer zu Schwabedissen HE, Nassif A, Modess C, Desta Z, Ogburn ET, et al. Impact of efavirenz on intestinal metabolism and transport: insights from an interaction study with ezetimibe in healthy volunteers. Clin Pharmacol Therap. 2012;91(3):506–13.

    Article  CAS  Google Scholar 

  68. Reyderman L, Kosoglou T, Boutros T, Seiberling M, Statkevich P. Pharmacokinetic interaction between ezetimibe and lovastatin in healthy volunteers. Curr Med Res Opin. 2004;20(9):1493–500.

    Article  CAS  PubMed  Google Scholar 

  69. Reyderman L, Kosoglou T, Statkevich P, Pember L, Boutros T, Maxwell SE, et al. Assessment of a multiple-dose drug interaction between ezetimibe, a novel selective cholesterol absorption inhibitor and gemfibrozil. Int J Clin Pharmacol Ther. 2004;42(9):512–8.

    Article  CAS  PubMed  Google Scholar 

  70. Reyderman L, Kosoglou T, Cutler DL, Maxwell S, Statkevich P. The effect of fluvastatin on the pharmacokinetics and pharmacodynamics of ezetimibe. Curr Med Res Opin. 2005;21(8):1171–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge Medela Canada Inc. for providing electric breast pumps for this study. They would also like to acknowledge the Lipid Clinic at St. Boniface Hospital for their contributions in arranging the collection of breast milk samples and storage, and completing patient questionnaires. This work was based on Cindy Hoi Ting Yeung’s thesis presented to the University of Waterloo in partial fulfilment of the requirement for the degree of Doctor of Philosophy in Pharmacy. A copy of the thesis is available from the University of Waterloo at https://libuwspaceprd02.uwaterloo.ca/bitstream/handle/10012/19412/Yeung_CindyHoiTing.pdf?isAllowed=y&sequence=7.

Author information

Authors and Affiliations

  1. Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, ON, Canada

    Cindy H. T. Yeung, Pooja Dalvi, Shinya Ito & Mehzabin Rahman

  2. Department of Clinical Pharmacology Unit, Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC, Canada

    Julie Autmizguine, Audrey Denoncourt & Yves Theoret

  3. Department of Pharmacology and Physiology, Universite de Montreal, Montreal, QC, Canada

    Julie Autmizguine

  4. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada

    Shinya Ito

  5. Division of Endocrinology and Metabolism, Department of Medicine, University of Manitoba, Winnipeg, MB, Canada

    Pamela Katz

  6. School of Pharmacy, University of Waterloo, 10 Victoria St S A, Kitchener, ON, N2G 1C5, Canada

    Andrea N. Edginton

Authors
  1. Cindy H. T. Yeung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Julie Autmizguine
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pooja Dalvi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Audrey Denoncourt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shinya Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pamela Katz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mehzabin Rahman
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yves Theoret
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andrea N. Edginton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea N. Edginton.

Ethics declarations

Funding

This research was funded by the Canadian Institutes of Health Research (CIHR) Project Grant PJT-159782, and CIHR Frederick Banting and Charles Best Canada Graduate Scholarships Doctoral Award (CGS-D), a Canada Scholarship to Honour Nelson Mandela, DF2-171445.

Conflicts of Interest

Cindy H.T. Yeung, Julie Autmizguine, Pooja Dalvi, Audrey Denoncourt, Shinya Ito, Pamela Katz, Mehzabin Rahman, Yves Theoret, and Andrea N. Edginton have no conflicts of interest to disclose relevant to this article.

Availability of Data and Material

A de-identified dataset can be shared with the appropriate approval. The requestor would need to contact the Principal Investigator (Dr. Shinya Ito, shinya.ito@sickkids.ca) with the request.

Ethics Approval

This study received ethics clearance from the REBs of the University of Manitoba (#HS19991) and the University of Waterloo (REB # 41155).

Informed Consent Statement

Informed consent was obtained from all individual participants included in the study.

Code Availability

Not applicable.

Author Contributions

CHTY, SI, and ANE conceptualized and designed the study. JA, AD, and YT developed the assay. PD, PK, and MR recruited patients and performed data collection. CHTY wrote the original draft manuscript. All authors reviewed and revised the manuscript.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 677 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yeung, C.H.T., Autmizguine, J., Dalvi, P. et al. Maternal Ezetimibe Concentrations Measured in Breast Milk and Its Use in Breastfeeding Infant Exposure Predictions. Clin Pharmacokinet 63, 317–332 (2024). https://doi.org/10.1007/s40262-023-01345-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40262-023-01345-0

Search

Navigation