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

Eur J Clin Pharmacol. 1984;27(2):159-63. doi: 10.1007/BF00544039.

Abstract

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 (beta t1/2) 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 beta t1/2 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 beta t1/2 after acute dosing. There was a significant correlation between creatinine clearance and acute beta t1/2 but there was considerable variability in individual patients and, even with severe degrees of renal impairment, major dose adjustments do not appear necessary.

MeSH terms

  • Acetylation
  • Adult
  • Aged
  • Blood Pressure / drug effects
  • Creatinine / metabolism
  • Female
  • Half-Life
  • Heart Rate / drug effects
  • Humans
  • Kidney Diseases / metabolism*
  • Kinetics
  • Male
  • Middle Aged
  • Phenotype
  • Pyridazines / metabolism*
  • Renal Dialysis

Substances

  • Pyridazines
  • BQ 22-708
  • Creatinine