The effects of renal impairment and age on the pharmacokinetics of
guanfacine were evaluated. In normal subjects,
guanfacine was found to be rapidly and completely absorbed, with an absolute bioavailability close to 100% and therefore no evidence of a noticeable first-pass effect. Its kinetics were best described by a 2-compartment model, with an elimination half-life of the beta phase of 17 hours. The major route of excretion was in the urine, with urinary excretion of 80% of a given dose within 4 days. Linearity of dose and thus predictability of blood levels were observed for single doses and at steady state. Although cumulative urinary excretion and renal clearance of unchanged
guanfacine were reduced in patients with
renal insufficiency, total clearances, serum levels, elimination rates constants and elimination half-lives differed very slightly, or at most by
a factor of 1.5 to 2 between patients with normal and severely impaired renal function. Age-related decreases in urinary excretion and renal clearance of
guanfacine were observed in 6 elderly patients and were accompanied by an increased proportion of metabolites to parent
drug, confirming the significant nonrenal clearance of the
drug. Based on pharmacokinetic studies in these target groups and on the dual renal and nonrenal clearance of
guanfacine, the
drug may, most probably, be administered to elderly patients and patients with
renal insufficiency without dosage adjustment.