Clinical Pharmacokinetics

, Volume 41, Issue 1, pp 7–17 | Cite as

Clinical Pharmacokinetics of Candesartan

  • Christoph H. GleiterEmail author
  • Klaus E. Mörike
Review Article Drug Disposition


Candesartan cilexetil is the prodrug of candesartan, an angiotensin II type 1 (AT1) receptor antagonist. Absorbed candesartan cilexetil is completely metabolised to candesartan. Oral bioavailability is low (about 40%) because of incomplete absorption. Plasma protein binding in humans is more than 99%. The volume of distribution in healthy individuals is 0.13 L/kg. CV-15959 is the inactive metabolite of candesartan.

Candesartan that reaches the systemic circulation is mainly cleared by the kidneys, and to a smaller extent by the biliary or intestinal route. The apparent oral clearance of candesartan is 0.25 L/h/kg after a single dose in healthy individuals. Oral clearance (3.4 to 28.4 L/h) is highly variable among patients. No relevant pharmacokinetic drug-food or drug-drug interactions are known. The terminal elimination half-life remains unclear, but appears to be longer than the currently used range of 4 to 9 hours.

Non-compartmental models do not appear to be appropriate for the analysis of candesartan pharmacokinetic data. A 2-compartment analysis revealed a much longer half-life of 29 hours using data from patients with hypertension. However, a further indepth analysis has never been performed. The concentration-effect relationship is unaffected by age. No gender or race differences have been shown in the effect or pharmacokinetics of candesartan.

Renal function affects the pharmacokinetic profile of candesartan. For patients with Creatinine clearances of >60 ml/min · 1.73m2, 30 to 60 ml/min · 1.73m2 and 15 to 30 ml/min · 1.73m2, the elimination half-life is 7.1, 10.0 and 15.7 hours, respectively, at a dose of 8 mg/day. However, at 12 mg/day an accumulation factor of 1.71 was found. Thus, a maximum daily dose of up to 8mg appears suitable in patients with severe renal dysfunction. No significant elimination of candesartan occurs with haemodialysis. In patients with mild to moderate hepatic impairment, no relevant pharmacokinetic alterations have been observed. Dosages of up to 12 mg/day do not require precautions in patients with mild to moderate liver disease.

Clinically effective dosages range between 8 and 32 mg/day. The response rate of monotherapy with candesartan in patients with hypertension increases with dosage, but never exceeds 60% at a daily dosage of 16mg of candesartan. Dosages up to 32 mg/day do not increase this response rate.



The authors were supported by a grant from the Bundesministerium für Bildung und Forschung (FKZ 01 EC 0001). The authors wish to thank Dr I. Meineke, from the Department of Clinical Pharmacology, University of Göttingen, Göttingen, Germany, for his helpful comments.


  1. 1.
    Burnier M, Brunner HR. Angiotensin II receptor antagonists. Lancet 2000; 355: 637–45PubMedCrossRefGoogle Scholar
  2. 2.
    McFayden RJ, Reid JL. Angiotensin receptor antagonists as a treatment for hypertension. J Hypertens 1994; 12: 1333–8Google Scholar
  3. 3.
    Siegl PKS, Kivlighn SD, Broten TP, et al. Pharmacology of angiotensin II receptor antagonists: comparison with renin inhibitors and angiotensin-converting enzyme inhibitors. Expert Opin Investig Drugs 1994; 3: 925–44CrossRefGoogle Scholar
  4. 4.
    McClellan KJ, Goa KL. Candesartan cilexetil: a review of its use in essential hypertension. Drugs 1998 Nov; 56(5): 847–69PubMedCrossRefGoogle Scholar
  5. 5.
    Swedberg K, Pfeffer M, Granger C, et al. Candesartan in heart failure — assessment of reduction in mortality and morbidity (CHARM): rationale and design. J Card Fail 1999; 5: 276–82PubMedCrossRefGoogle Scholar
  6. 6.
    McKelvie RS, Yusuf S, Pericak D, et al. Comparison of candesartan, enalapril, and their combination in congestive heart failure: Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study. Circulation 1999; 100: 1056–64PubMedCrossRefGoogle Scholar
  7. 7.
    Riegger GAJ, Bouzo H, Petr P, et al. Improvement in exercise tolerance and symptoms of congestive heart failure during treatment with candesartan cilexetil. Circulation 1999; 100: 2224–30PubMedCrossRefGoogle Scholar
  8. 8.
    Mogensen CE, Neldam S, Tikkanen I, et al., CALM group. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ 2000; 321: 1440–4PubMedCrossRefGoogle Scholar
  9. 9.
    Miyabayashi T, Okuda T, Motohashi M, et al. Quantitation of a new potent angiotensin II receptor antagonist, TCV-116, and its metabolites in human serum and urine. J Chromatogr 1996; 677: 123–32CrossRefGoogle Scholar
  10. 10.
    Stenhoff H, Lagerström PO, Andersen C. Determination of candesartan cilexetil, candesartan and a metabolite in human plasma and urine by liquid chromatography and fluorometric detection. J Chromatogr B Biomed Sci Appl 1999; 731: 411–7PubMedCrossRefGoogle Scholar
  11. 11.
    Lee JW, Naidong W, Johnson T, et al. Development and validation of column-switching high-performance Chromatographic methods for the determination of a potent All receptor antagonist, TCV-116, and its metabolites in human serum and urine. J Chromatogr 1995; 670: 287–98CrossRefGoogle Scholar
  12. 12.
    Burnier M, Buclin T, Biollaz J, et al. Pharmacokinetic-pharmacodynamic relationships of three angiotensin II receptor antagonists in normal volunteers. Kidney Int 1996; 49 Suppl. 55: S24–9Google Scholar
  13. 13.
    Delacretaz E, Nussberger J, Biollaz J, et al. Characterization of the angiotensin II receptor antagonist TCV-116 in healthy volunteers. Hypertension 1995; 25: 14–25PubMedCrossRefGoogle Scholar
  14. 14.
    Van Lier JJ, van Heiningen PNM, Sunzel M. Absorption, metabolism and excretion of 14C-candesartan and 14C-candesartan cilexetil in healthy volunteers. J Hum Hypertens 1997; 11 Suppl. 2: S27–8PubMedGoogle Scholar
  15. 15.
    Pfister M, Schaedeli F, Frey FJ, et al. Pharmacokinetics and haemodynamics of candesartan cilexetil in hypertensive patients on regular haemodialysis. Br J Clin Pharmacol 1999; 47: 645–51PubMedCrossRefGoogle Scholar
  16. 16.
    Taavitsainen P, Kiukaanniemi K, Pelkonen O. In vitro screening of human hepatic P450 enzymes by five angiotensin-II receptor antagonists. Eur J Clin Pharmacol 2000; 56: 135–40PubMedCrossRefGoogle Scholar
  17. 17.
    Hoogkamer JFW, Kleinbloesem CH, Ouwerkerk M, et al. Pharmacokinetics and safety of candesartan cilexetil in subjects with normal and impaired liver function. Eur J Clin Pharmacol 1998; 54: 341–5PubMedCrossRefGoogle Scholar
  18. 18.
    Riddell JG. Bioavailability of candesartan is unaffected by food in healthy volunteers administered candesartan cilexetil. J Hum Hypertens 1997; 11 Suppl. 2: S29–30PubMedGoogle Scholar
  19. 19.
    Ogihara T, Mikami H, Higaki J. Clinical application of a new potent angiotensin II receptor antagonist, TCV-116. Rinsho Iyaku 1993; 9: 1031–63Google Scholar
  20. 20.
    Jonkman JHG, van Lier JJ, van Heiningen PNM, et al. Pharmacokinetic drug interaction studies with candesartan cilexetil. J Hum Hypertens 1997; 11 Suppl. 2: S31–5PubMedGoogle Scholar
  21. 21.
    Azizi M, Chatellier G, Guyene T-T, et al. Pharmacokinetic-pharmacodynamic interactions of candesartan cilexetil and losartan. J Hypertens 1999; 17: 561–8PubMedCrossRefGoogle Scholar
  22. 22.
    Meineke I, Feltkamp H, Högemann A, et al. Pharmacokinetics and pharmacodynamics of candesartan after administration of its pro-drug candesartan cilexetil in patients with mild to moderate essential hypertension — a population analysis. Eur J Clin Pharmacol 1997; 53: 221–8PubMedCrossRefGoogle Scholar
  23. 23.
    Zuschke CA, Keys I, Munger MA, et al. Candesartan cilexetil: a comparison of once-daily versus twice-daily administration for systemic hypertension. Clin Ther 1999; 21: 464–7PubMedCrossRefGoogle Scholar
  24. 24.
    Hübner R, Hogemann AM, Sunzel M, et al. Pharmacokinetics of candesartan after single and repeated doses of candesartan cilexetil in young and elderly healthy volunteers. J Hum Hypertens 1997; 11 Suppl. 2: S19–25PubMedGoogle Scholar
  25. 25.
    Bell TP, DeQuattro V, Lasseter KC, et al. Effective dose range of candesartan cilexetil for systemic hypertension. Am J Cardiol 1999; 83: 272–5PubMedCrossRefGoogle Scholar
  26. 26.
    Buter H, Navis GY, Woittiez AJJ, et al. Pharmacokinetics and pharmacodynamics of candesartan cilexetil in patients with normal to severely impaired renal function. Eur J Clin Pharmacol 1999; 54: 953–8PubMedCrossRefGoogle Scholar
  27. 27.
    De Zeeuw D, Remuzi G, Kirch W. Pharmacokinetics of candesartan cilexetil in patients with renal or hepatic impairment. J Hum Hypertens 1997; 11 Suppl. 2: S37–42PubMedGoogle Scholar
  28. 28.
    Csajka C, Buclin T, Biollaz J, et al. Pharmacokinetic-pharmacodynamic profile of angiotensin II receptor antagonists. Clin Pharmacokinet 1997; 32: 1–29PubMedCrossRefGoogle Scholar
  29. 29.
    Malerczyk C, Fuchs B, Belz GG, et al. Angiotensin II antagonism and plasma radioreceptor-kinetics of candesartan in man. Br J Clin Pharmacol 1998; 45: 567–73PubMedCrossRefGoogle Scholar
  30. 30.
    Lacourciere Y, Asmar R, CHAMP Study Group. Comparison of the effects of candesartan and losartan on ambulatory blood pressure in patients with essential ambulatory hypertension: a forced titration study [abstract]. Am J Hypertens 1999; 12: 41ACrossRefGoogle Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  1. 1.Abteilung Klinische PharmakologieUniversitätsklinikum TübingenTübingenGermany

Personalised recommendations