Disposition of 14C-guanabenz in patients with essential hypertension*

Capsules containing either 16 or 32 mg of 14C-guanabenz were given to 8 hypertensive patients. Maximum concentrations of guanabenz in plasma (1.2 to 5.2 ng/ml) were reached at 2 to 5 hr after dosing. 14C elimination into urine was 79.7 ± 10.6% (SD) and 76.7 ± 7.4% of the dose after the 16- and 32-mg doses, respectively, while guanabenz accounted for less than 1% after either dose. Kinetic parameters for guanabenz were estimated by fitting the plasma and urinary data to a 2-compartment model. After the 16-mg dose, the elimination half-life (t½) was 14 ± 5 hr, volume of distribution in the central compartment (Vc) was 5.0 ± 2.2 kl, and total plasma clearance (Clp) was 8 ± 4 l/min. After the 32-mg dose, t½ was 12 ± 3 hr, Vc was 7.5 ± 1.8 kl, and Clp, was 17 ± 6 l/min. No statistically significant difference, except of total plasma clearance, was observed between any of the parameters followed after the 2 doses. (E)-p-Hydroxyguanabenz (unconjugated and as a glucuronide) was the major metabolite and accounted for 35.4 ± 3.0% of the urinary radioactivity. Minor amounts of guanabenz and 2,6-dichlorobenzyl alcohol after β-glucuronidase hydrolysis indicated that N-glucuronidation and cleavage at the benzol carbon were minor metabolic pathways. The drug effectively lowered blood pressure in the hypertensive patients; no other significant effects were noted. Clinical Pharmacology and Therapeutics (1980) 27, 44–52; doi:10.1038/clpt.1980.7