Skip to main content
Log in

Clinical Pharmacokinetics of Amlodipine

  • Review Article
  • Drug Disposition
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

Amlodipine is a dihydropyridine calcium antagonist drug with distinctive pharmacokinetic characteristics which appear to be attributable to a high degree of ionisation. Following oral administration, bioavailability is 60 to 65% and plasma concentrations rise gradually to peak 6 to 8h after administration. Amlodipine is extensively metabolised in the liver (but there is no significant presystemic or first-pass metabolism) and is slowly cleared with a terminal elimination half-life of 40 to 50h. Volume of distribution is large (21 L/kg) and there is a high degree of protein binding (98%). There is some evidence that age, severe hepatic impairment and severe renal impairment influence the pharmacokinetic profile leading to higher plasma concentrations and longer half-lives. There is no evidence of pharmacokinetic drug interactions. Amlodipine shows linear dose-related pharmacokinetic characteristics and, at steady-state, there are relatively small fluctuations in plasma concentrations across a dosage interval.

Thus, although structurally related to other dihydropyridine derivatives, amlodipine displays significantly different pharmacokinetic characteristics and is suitable for administration in a single daily dose.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abernethy DR. The pharmacokinetic profile of amlodipine. American Heart Journal 118: 110–1103, 1989

    Article  Google Scholar 

  • Abernethy DR, Gutkowska J, Lambert MD. Amlodipine in elderly hypertensive patients: pharmacokinetics and pharmacodynamics. Journal of Cardiovascular Pharmacology 12 (Suppl. 7): S67–S71, 1988

    Article  PubMed  Google Scholar 

  • Abernethy DR, Gutkowska J, Winterbottom LA. Effects of amlodipine, a long-acting dihydropyridine calcium antagonist in aging hypertension: pharmacodynamics in relation to disposition. Clinical Pharmacology and Therapeutics 48: 76–86, 1990

    Article  PubMed  CAS  Google Scholar 

  • Beresford AP, Humphrey MJ, Stopher DA. Amlodipine, a calcium channel blocker with pharmacokinetic properties novel to dihydropyridines. British Journal of Pharmacology 85 (Suppl.): 333, 1985

    Google Scholar 

  • Beresford AP, Macrae PV, Stopher DA, Wood BA. Analysis of amlodipine in human plasma by gas chromatography. Journal of Chromatography 420: 178–183, 1987

    Article  PubMed  CAS  Google Scholar 

  • Beresford AP, McGibney D, Humphrey MJ, Macrae PV, Stopher DA. Metabolism and kinetics of amlodipine in man. Xenobiotica 18: 245–254, 1988

    Article  PubMed  CAS  Google Scholar 

  • Bremner AD, Fell PJ, Hosie J, James IGV, Saul PA, et al. Side-effects of dihydropyridine therapy: comparison of amlodipine and nifedipine retard. Journal of Human Hypertension, in press, 1991

    Google Scholar 

  • Burris JF, Ames RP, Applegate WB, Ram CVS, Davidov ME, et al. Double-blind comparison of amlodipine and hydrochlorothiazide in patients with mild to moderate hypertension. Journal of Cardiovascular Pharmacology 12 (Suppl. 7): S98–S102, 1988

    Article  PubMed  Google Scholar 

  • Elliott HL, Meredith PA, Howie CA, Donnelly R. Concentration effect relationships for amlodipine in essential hypertensives. Clinical Pharmacology and Therapeutics, in press, 1991

    Google Scholar 

  • Elliott HL, Meredith PA, Reid JL, Faulkner JK. A comparison of the disposition of single oral doses of amlodipine in young and elderly subjects. Journal of Cardiovascular Pharmacology 12 (Suppl. 7): S64–S66, 1988

    Article  PubMed  CAS  Google Scholar 

  • Faulkner JK, Hayden ML, Chasseaud LF, Taylor T. Absorption of amlodipine unaffected by food: solid dose equivalent to solution dose. Arzneimittel-Forschung 39: 799–801, 1989

    PubMed  CAS  Google Scholar 

  • Faulkner JK, McGibney D, Chasseaud LF, Perry JL, Taylor IW. The pharmacokinetics of amlodipine in healthy volunteers after single intravenous and oral doses and after 14 repeated oral doses given once daily. British Journal of Clinical Pharmacology 22: 21–25, 1986

    Article  PubMed  CAS  Google Scholar 

  • Frick MH, McGibney D, Tyler HM. A dose-response study of amlodipine in mild to moderate hypertension. Journal of Internal Medicine 225: 101–105, 1989

    Article  PubMed  CAS  Google Scholar 

  • Glasser SP, Chrysant SG, Graves J, Rofman B, Koehn DK. Safety and efficacy of amlodipine added to hydrochlorothiazide therapy in essential hypertension. American Journal of Hypertension 2: 154–157, 1989

    PubMed  CAS  Google Scholar 

  • Kleinbloesem CH, van Brummelen P, Breimar DD. Nifedipine: relationship between pharmacokinetics and pharmacodynamics. Clinical Pharmacokinetics 12: 12–29, 1987

    Article  PubMed  CAS  Google Scholar 

  • Laher MS, Kelly JG, Doyle GD, Carmody M, Donohoe JF, et al. Pharmacokinetics of amlodipine in renal impairment. Journal of Cardiovascular Pharmacology 12 (Suppl. 7): S60–S63, 1988

    Article  PubMed  Google Scholar 

  • Maclean D, Mitchell ET, Wilcox RG, Walker P, Tyler HM. Amlodipine and captopril in moderate-severe essential hypertension. Journal of Human Hypertension 2: 127–132, 1988

    PubMed  CAS  Google Scholar 

  • Mason RP, Campbell SF, Wang S-D, Herbette LG. Comparison of location and binding for the positively charged 1,4-dihydropyridine calcium channel antagonist amlodipine with uncharged drugs of this class in cardiac membranes. Molecular Pharmacology 36: 634–640, 1989

    PubMed  CAS  Google Scholar 

  • Meredith, PA, Elliott HL, Howie CA. The pharmacokinetics and pharmacodynamics of amlodipine and felodipine ER in borderline hypertensives. British Journal of Clinical Pharmacology, in press, 1991

    Google Scholar 

  • Miller SHK, McSharry DR. An automated gas chromatography assay for amlodipine. Journal of Chromatography, in press, 1991

    Google Scholar 

  • Mroczek WJ, Burris JF, Allenby KS. A double-blind evaluation of the effect of amlodipine on ambulatory blood pressure in hypertensive patients. Journal of Cardiovascular Pharmacology 12 (Suppl. 7): S79–S84, 1988

    Article  PubMed  Google Scholar 

  • Rofman BA. Long-term open evaluation of amlodipine vs hydrochlorothiazide in patients with essential hypertension. Journal of Cardiovascular Pharmacology 12 (Suppl. 7): S94–S97, 1988

    Article  PubMed  Google Scholar 

  • Schwartz JB. Effects of amlodipine on steady-state digoxin concentrations and renal digoxin clearance. Journal of Cardiovascular Pharmacology 12: 1–5, 1988

    Article  PubMed  CAS  Google Scholar 

  • Stopher DA, Beresford AP, Macrae PV, Humphrey MJ. The metabolism and pharmacokinetics of amlodipine in humans and animals. Journal of Cardiovascular Pharmacology 12 (Suppl. 7): S55–S59, 1988

    Article  PubMed  CAS  Google Scholar 

  • Webster J, Robb OB, Jeffers TA, Scott AK, Petrie JC, et al. Once daily amlodipine in the treatment of mild to moderate hypertension. British Journal of Clinical Pharmacology 24: 713–719, 1987

    Article  PubMed  CAS  Google Scholar 

  • Williams DM, Cubeddu L. Amlodipine pharmacokinetics in healthy volunteers. Journal of Clinical Pharmacology 28: 990–994, 1988

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meredith, P.A., Elliott, H.L. Clinical Pharmacokinetics of Amlodipine. Clin-Pharmacokinet 22, 22–31 (1992). https://doi.org/10.2165/00003088-199222010-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-199222010-00003

Keywords

Navigation