European Journal of Clinical Pharmacology

, Volume 27, Issue 2, pp 159–163 | Cite as

Clinical pharmacological studies with the vasodilator endralazine in patients with renal impairment

  • H. L. Elliott
  • P. A. Meredith
  • L. Sloan
  • J. L. Reid


The influence of renal impairment on the pharmacokinetics of endralazine was studied in 12 patients; 4 patients on regular haemodialysis therapy (creatinine clearance less than 5 ml/min) and 8 patients with varying degrees of renal impairment (creatinine clearance 11–52 ml/min). Following an oral dose of 10 mg endralazine the mean terminal elimination half-life (βt1/2) in the dialysis sub-group was prolonged at 7.1 h (range 3.3 to 14 h), compared to 3.6 h in the other renal patients (and compared to 2.3 h in hypertensive patients with normal renal function). After one week's therapy with 10 mg B.D. endralazine in the 8 patients with moderate renal impairment there was a significant increase in βt1/2 to 8.6 h but there was no significant change in the area under the drug concentration-time curve and no evidence of drug accumulation. In this study those patients with the poorest renal function had the longest βt1/2 after acute dosing. There was a significant correlation between creatinine clearance and acute βt1/2 but there was considerable variability in individual patients and, even with severe degrees of renal impairment, major dose adjustments do not appear necessary.

Key words

endralazine renal impairment pharmacokinetics 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Elliott HL, McLean K, Sumner DJ, Donnelly RJ, Reid JL (1982) Clinical evaluation of endralazine (BQ 22708) a new vasodilator, in essential hypertension. Clin Exp Hypertens 4 [8]: 1409–1418Google Scholar
  2. 2.
    Kirch W, Axthelm T (1982) Endralazine, a new peripheral vasodilator — a randomised crossover trial against dihydralazine. J Cardiovasc Pharmacol 4: 562–566Google Scholar
  3. 3.
    Bogers WAJL, Meems L (1983) Endralazine, a new peripheral vasodilator. Evaluation of safety and efficacy over a 3 year period. Eur J Clin Pharmacol 24: 301–305Google Scholar
  4. 4.
    Holmes DG, Bogers WAJL, Wideroe T-E, Huunan-Seppala A, Wideroe B (1983) Endralazine, a new peripheral vasodilator: absence of effect of acetylator status on antihypertensive effect. Lancet 1: 670–671Google Scholar
  5. 5.
    Reece PA, Cozamanis I, Zacest R (1982) Influence of acetylator phenotype on the pharmacokinetics of a new vasodilator antihypertensive, endralazine. Eur J Clin Pharmacol 23: 523–527Google Scholar
  6. 6.
    Meredith PA, Elliott HL, McSharry D, Kelman AW, Reid JL (1983) The Pharmacokinetics of endralazine in essential hypertensives and in normotensive subjects. Br J Clin Pharmacol 16: 27–32Google Scholar
  7. 7.
    Reece PA, Cozamanis I, Zacest R (1981) A sensitive HPLC assay for endralazine and two of its main metabolites in human plasma. J Chromatog 225: 151–160Google Scholar
  8. 8.
    Carr K, Oates JA, Nies AS, Woosley RL (1978) Simultaneous analysis of dapsone and monoacetyl dapsone employing HPLC: a rapid method for determining acetylator phenotype. Br J Clin Pharmacol 6: 421–427Google Scholar
  9. 9.
    Wegmuller E, Reubi FC (1983) Changes in renal function induced by endralazine, a new antihypertensive drug. Eur J Clin Pharmacol 24: 307–314Google Scholar
  10. 10.
    Simon P, Meyrier A, Brissot P (1981) Uraemia and the liver — II. Drugs and the liver in the uraemic patient. Nephron 29: 7–13Google Scholar
  11. 11.
    Talseth T (1977) Clinical pharmacokinetics of hydralazine. Clin Pharmacokinet 2: 317–329Google Scholar
  12. 12.
    Chaignon M, le Roux E, Aubert Ph, Lucsko M, Safar M, Flouvat B, Guedon J (1981) Clinical pharmacology of prazosin in hypertensive patients with chronic renal failure. J Cardiovasc Pharmacol 3: 151–160Google Scholar
  13. 13.
    Bianchetti G, Graziani G, Brancaccio D, Morganti A, Leonetti G, Manfrin M, Sega R, Ponticelli C, Morselli PL (1976) Pharmacokinetics and effects of propranolol in terminal uraemic patients and in patients undergoing regular dialysis treatment. Clin Pharmacokinet 1: 373–384Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • H. L. Elliott
    • 1
  • P. A. Meredith
    • 1
  • L. Sloan
    • 1
  • J. L. Reid
    • 1
  1. 1.Department of Materia MedicaStobhill General HospitalGlasgowScotland

Personalised recommendations