Pharmacokinetics and metabolism of guanfacine in man: a review.

The fate of guanfacine has been investigated extensively in animals. Pharmacokinetics and metabolism of [C]-guanfacine were studied in fourteen subjects given 3 mg orally (seven subjects) and 2.3 mg intravenously. Plasma levels and urinary excretion of radioactivity were measured by liquid scintillation counting. Parent drug was determined by gas chromatography-mass spectrometry. The analytical results were submitted to pharmacokinetic evaluation using the SAAM 26 programme. Metabolites in urine were identified by high pressure liquid chromatography. Guanfacine was rapidly and completely absorbed. Its absolute bioavailability was close to 100%, no evidence of any first-pass effect being found. Its distribution was characterized by low blood levels, low plasma protein binding and a relatively high affinity to the tissues ( of 300 l). The elimination half-life of the β-phase was 17 hours. The major route of excretion (80% of the dose) was in the urine. About 1/3 to 1/4 of the total clearance of 11 l/h was renal. The principal metabolite was the 3-hydroxy-derivative of guanfacine conjugated as either -glucuronide or -sulphate. The important fraction (30%) of parent drug found in the urine demonstrates a rather moderate biotransformation of guanfacine in man. The results of an additional study after multiple dosing showed that the measured steady-state plasma levels were in agreement with the values predicted from a single dose experiment and proportional to the daily dosage.