Skip to main content
SpringerLink
Log in

Evaluation of a Pharmacokinetic Interaction between Telmisartan and Chlorthalidone in Healthy Male Adult Subjects

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

Abstract

Background and Objective

Combination therapy is recommended for the effective management of hypertension according to most treatment guidelines, including those of the US Joint National Committee. Therefore, pharmacokinetic drug interactions are an important issue in combination therapy for hypertension. In this study, the pharmacokinetic properties of telmisartan and chlorthalidone were evaluated to investigate their pharmacokinetic interactions in healthy subjects.

Methods

Two separate, randomized, multiple-dose, two-period, one-sequence studies were conducted. In study A, 43 participants received 80 mg of telmisartan orally for 7 days, and were then administered oral chlorthalidone 25 mg for 14 days (days 8–21), coadministered with 80 mg of telmisartan from day 15. In study B, 14 participants received oral chlorthalidone (25 mg) for 13 days, followed by coadministration with 80 mg of telmisartan orally for 7 days.

Results

The geometric mean ratios (GMRs) (90 % confidence intervals [CIs]) of the maximum plasma concentration (C max,ss) and area under the concentration-time curve for the dosing interval at steady state (AUCτ,ss) of telmisartan (with and without chlorthalidone) were 1.018 (0.861–1.203) and 1.099 (1.015–1.190), respectively. For chlorthalidone (with/without telmisartan), the GMRs (90 % CIs) for C max,ss and AUCτ,ss were 0.996 (0.922–1.075) and 0.992 (0.925–1.064), respectively. The GMRs and 90 % CIs for telmisartan and chlorthalidone were all within the 0.80–1.25 range.

Conclusion

Thus, in this study, there was no significant pharmacokinetic interaction between telmisartan and chlorthalidone.

ClinicalTrial.gov identifier

NCT01806363.

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. Maillard MP, Burnier M. Is the fixed-dose combination of telmisartan and hydrochlorothiazide a good approach to treat hypertension? Vascular Health Risk Manage. 2007;3(3):265–78.

    CAS  Google Scholar 

  2. Keating GM. Losartan/hydrochlorothiazide: a review of its use in the treatment of hypertension and for stroke risk reduction in patients with hypertension and left ventricular hypertrophy. Drugs. 2009;69(9):1239–65.

    Article  CAS  PubMed  Google Scholar 

  3. Sharpe M, Jarvis B, Goa KL. Telmisartan: a review of its use in hypertension. Drugs. 2001;61(10):1501–29.

    Article  CAS  PubMed  Google Scholar 

  4. Karlberg BE, Lins L-E, Hermansson K. Efficacy and safety of telmisartan, a selective AT1 receptor antagonist, compared with enalapril in elderly patients with primary hypertension. J Hypertension. 1999;17:293–302.

    Article  CAS  Google Scholar 

  5. Freytag F, Schelling A, Meinicke T, Deichsel G, for the Telmisartan Hypertension Experience in a Randomized European Study Versus Atenolol Study Group. Comparison of 26-week efficacy and tolerability of telmisartan and atenolol, in combination with hydrochlorothiazide as required, in the treatment of mild to moderate hypertension: a randomized, multicenter study. Clin Ther. 2001;23(1):108–23.

  6. Stangier J, Su C, Roth W. Pharmacokinetics of orally and intravenously administered telmisartan in healthy young and elderly volunteers and in hypertensive patients. J Int Med Res. 2000;28:149–67.

    Article  CAS  PubMed  Google Scholar 

  7. Tatami S, Sarashina A, Yamamura N, et al. Population pharmacokinetics of an angiotensin II receptor antagonist, telmisartan, in healthy volunteers and hypertensive patients. Drug Metab Pharmacokinet. 2003;18(3):203–11.

    Article  CAS  PubMed  Google Scholar 

  8. Stangier J, Su CA, Hendricks MG, et al. The effect of telmisartan on the steady-state pharmacokinetics of digoxin in healthy male volunteers. J Clin Pharmacol 2000;40(12 Pt1):1373–9.

  9. Israili ZH. Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. J Hum Hypertens (Suppl). 2000;14:S73–86.

    Article  CAS  Google Scholar 

  10. Unger T, Kaschina E. Drug interactions with angiotensin receptor blockers: a comparison with other antihypertensives. Drug Saf. 2003;26(10):707–20.

    Article  CAS  PubMed  Google Scholar 

  11. Mallat SG. What is a preferred angiotensin II receptor blocker-based combination therapy for blood pressure control in hypertensive patients with diabetic and non-diabetic renal impairment? Cardiovasc Diabetol. 2012;10(11):32.

    Article  Google Scholar 

  12. Gradman AH. Rationale for triple-combination therapy for management of high blood pressure. J Clin Hypertens. 2010;12(11):869–78.

    Article  Google Scholar 

  13. Carter BL, Ernst ME, Cohen JD. Hydrochlorothiazide versus chlorthalidone: evidence supporting their interchangeability. Hypertension. 2003;43:4–9.

    Article  PubMed  Google Scholar 

  14. Sica DA, Carter B, Cushman W. Thiazide and loop diuretics. J Clin Hypertens. 2011;13(9):639–43.

    Article  CAS  Google Scholar 

  15. Sica DA. Chlorthalidone: a renaissance in use? Exp Opin Pharmacother. 2009;10(13):2037–9.

    Article  CAS  Google Scholar 

  16. Sica D, Bakris GL, White WB, et al. Blood pressure-lowering efficacy of the fixed-dose combination of azilsartan medoxomil and chlorthalidone: a factorial study. J Clin Hypertens. 2012;14(5):284–92.

    Article  CAS  Google Scholar 

  17. Cheng JW. Azilsartan/chlorthalidone combination therapy for blood pressure control. Integr Blood Press Control. 2013;6:39–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). J Am Med Assoc. 2014;311(5):507–20.

    Article  CAS  Google Scholar 

  19. World Medical Association. World Medical Association Declaration of Helsinki ethical principles for medical research involving human subjects. J Am Med Assoc. 2013;310(20):2191–4.

    Article  Google Scholar 

  20. ICH harmonised tripartite guideline: guideline for good clinical practice E6 (R1). International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use. 1996. Available at: http://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html. Accessed 12 Apr 2016.

  21. Guideline for the validation of bioanalytical method. Ministry of Food and Drug Safety. Republic of Korea, 2010. Available at: http://www.mfds.go.kr/index.do?mid=689&pageNo=46&seq=7560&cmd=v. Accessed 15 Nov 2015.

  22. Guidance for industry: Drug interaction studies: study design, data analysis, implications for dosing, and labeling recommendations [draft guidance]. FDA Center for Drug Evaluation and Research. Silver Spring, MD: FDA, 2012. Available at: http://www.fda.gov/drugs/GuidanceComplianceRegulatoryInformation/guidances/default.htm. Accessed 15 Nov 2015.

  23. Wagstaff AJ. Valsartan/hydrochlorothiazide: a review of its use in the management of hypertension. Drugs. 2006;66(14):1881–901.

    Article  CAS  PubMed  Google Scholar 

  24. McCrea JB, Lo MW, Tomasko L, et al. Absence of a pharmacokinetic interaction between losartan and hydrochlorothiazide. J Clin Pharmacol. 1995;35(12):1200–6.

    Article  CAS  PubMed  Google Scholar 

  25. McGill JB, Reilly PA. Telmisartan plus hydrochlorthiazide versus telmisartan or hydrochlorothiazide monotherapy in patients with mild to moderate hypertension: a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. Clin Ther. 2001;23(6):833–50.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

Drs. S.J. Seong and Ms. Lim contributed equally to this work. This study was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (HI15C0001, HI14C1731, A070001, HI13C1232), the Industrial Core Technology Development Program (10051129, Development of the system for ADME assessment using radiolabeled compounds) funded by the Ministry of Trade, Industry and Energy (MOTIE, Korea), and the Bio and Medical Technology Development Program of the National Research Foundation, funded by the Ministry of Science, ICT and Future Planning, Republic of Korea (NRF-2013M3A9B6046416).

Author information

Author notes

    Authors and Affiliations

    1. Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Cell and Matrix Research Institute and Clinical Trial Center, Kyungpook National University Graduate School and Hospital, Daegu, Republic of Korea

      Sook Jin Seong, Joomi Lee, Boram Ohk, Mi-Ri Gwon, Bo Kyung Kim, Hyun-Ju Kim, Hae Won Lee, Woo Youl Kang & Young-Ran Yoon

    2. College of Pharmacy, Yeungnam University, Kyungsan, Kyungpook, Republic of Korea

      Mi-sun Lim

    3. Division of Cardiology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea

      Dong Heon Yang

    Authors
    1. Sook Jin Seong
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Mi-sun Lim
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Joomi Lee
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Boram Ohk
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Mi-Ri Gwon
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Bo Kyung Kim
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Hyun-Ju Kim
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Dong Heon Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Hae Won Lee
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Woo Youl Kang
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Young-Ran Yoon
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Young-Ran Yoon.

    Ethics declarations

    Funding

    This study was funded by HanAll BioPharma Co., Ltd., Seoul, Republic of Korea.

    Conflict of interest

    SJS, MSL, JL, BO, MRG, BKK, HJK, DHY, HWL, WYK and YRY have no conflicts of interest that are relevant to the content of this manuscript.

    Ethical approval

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

    Informed consent

    All volunteers received a full explanation regarding the study and submitted a written informed consent before a screening test for eligibility in the study.

    Additional information

    S. J. Seong and M. Lim equally contributed to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Seong, S.J., Lim, Ms., Lee, J. et al. Evaluation of a Pharmacokinetic Interaction between Telmisartan and Chlorthalidone in Healthy Male Adult Subjects. Clin Drug Investig 36, 613–623 (2016). https://doi.org/10.1007/s40261-016-0406-y

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s40261-016-0406-y

    Keywords

    Search

    Navigation