The influence of renal function on clinical pharmacokinetics of moxonidine.

Investigations were carried out on 24 hypertensive or borderline hypertensive patients with different degrees of renal function. Eight had normal renal function [glomerular filtration rate (GFR) greater than 90 ml/min], 8 moderate (GFR 30 to 60 ml/min) and 8 severe renal impairment (GFR less than 30 ml/min). All patients were given moxonidine 0.3mg once daily for 7 days and both pharmacokinetic and pharmacodynamic data were determined. During moxonidine treatment plasma elimination half-life, area under the plasma concentration-time curve (AUC) and apparent total clearance (CLT) showed statistically significant differences among patients in the 3 groups. Elimination half-life was 2.6 +/- 0.9 hours in patients with a GFR greater than 90 ml/min and increased to 6.9 +/- 3.7 hours in those with a GFR less than 30 ml/min (mean +/- SD; p = 0.012). Correspondingly, AUC0-24 h rose from 5.4 +/- 2.7 to 17.2 +/- 7.9 micrograms/L . h (p = 0.001), and CLT decreased from 1150 +/- 602.l ml/min to 369 +/- 227.6 ml/min (p = 0.001). These data suggest that once-daily administration of 0.3mg moxonidine may be appropriate in patients with impaired renal function. Independent of renal function, moxonidine was well tolerated in 22 of 24 patients. No deterioration in renal function as a consequence of the use of moxonidine was found. Thus, in patients with renal failure, dosage of moxonidine should be individually titrated according to the desired clinical response, as is recommended for hypertensive patients without renal impairment.