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Absorption, distribution, elimination and metabolism of 14C-heptaminol hydrochloride in rat.

Absorption, distribution, excretion and metabolism studies with 14C-labelled 6-amino-2-methyl-2-heptanol hydrochloride (14C-heptaminol hydrochloride, Hept-amyl) were carried out in rat. After a 10 mg/kg p.o. dose heptaminol was rapidly and entirely absorbed. Following the administration of 8 mg/kg i.v. or 12 mg/kg p.o., all tissues studied, except brain, contained higher levels of radioactivity than did plasma. No evidence of accumulation of the drug was seen in any tissue. Whole-body autoradiography revealed a preferential localisation in salivary glands, hypophysis and adrenal medulla 1 h after a 10 mg/kg i.v. or p.o. dose. Brain autoradiography showed radioactivity localised only in highly vascularised areas (choroid plexus and pia mater). Excretion occurred mainly by kidney, 68% of the radioactivity being excreted in urine 4 h after a dose of 10 mg/kg i.v. Biliary and faecal elimination accounted for less than 1% of the radioactivity administered. Heptaminol was metabolized to a hydroxylated metabolite, 6-amino-2-methyl-1,2-heptanediol, which was excreted unconjugated in urine. As doses increased from 10 to 200 mg/kg p.o., the amount of metabolite excreted in the 24-h urines decreased from 7.05% to 4.24% of the urinary radioactivity, indicating a saturation of the metabolism at high doses. Pretreatment of rats with phenobarbital increased the percentage of metabolite excreted in urine, but was unable to prevent the saturation of the metabolism at high doses of heptaminol.