Clinical pharmacological studies with the vasodilator endralazine in patients with renal impairment.
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.
D000107:Acetylation; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011724:Pyridazines / Q000378:metabolism*; D006435:Renal Dialysis
D011724:Pyridazines; C014926:BQ 22-708; D003404:Creatinine