Pharmacokinetics of guanfacine in patients with impaired renal function and in some elderly patients.
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.
D000042:Absorption; D058186:Acute Kidney Injury / Q000150:complications / Q000378:metabolism*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000375:Aging; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D004341:Drug Evaluation; D005260:Female; D005919:Glomerular Filtration Rate; D016316:Guanfacine; D006146:Guanidines / Q000378:metabolism* / Q000627:therapeutic use / Q000652:urine; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010648:Phenylacetates / Q000378:metabolism* / Q000627:therapeutic use / Q000652:urine; D011485:Protein Binding
D001798:Blood Proteins; D006146:Guanidines; D010648:Phenylacetates; D016316:Guanfacine