Absorption, Distribution and Excretion of ¹⁴C-Labelled 6, 6, 9-Trimethyl-9-azabicyclo [3, 3, 1] non-3β-yl α, α-di (2-thienyl) glycolate Hydrochloride Monohydrate (PG-501)

Abstract

Absorption, distribution, and excretion of ¹⁴C-labelled 6, 6, 9-trimethyl-9-azabicyclo-[3, 3, 1] non-3β-yl α, α-di (2-thienyl) glycolate hydrochloride monohydrate (PG-501), which has a potent anti-parkinsonian action, were studied in the rats and mice by means of whole-body autoradiographic procedure and the tracer technique. The orally administered drug reached a maximum plasma level at 30 min in the rat. The time course of absorption showed two phases, a rapid phase with a half-life of about 5.8 min and a slow phase with that of 138 min. The distribution of N-¹⁴CH₃-PG-501 in the mouse after oral administration showed that the radioactivity was concentrated in tissues of the brain, liver, intestine, lung, Harder's gland, salivary gland, and kidneys. When the drug was administered intravenously to the mouse, high radioactivity was found in the brown fat, salivary gland, Harder's gland, and adrenal cortex. This drug was rapidly taken up in the brain and passed through the placental barrier. Excretion of radioactivity was about 25% in urine, 8% in feces, and 37% in the expired air within 24 hr and about 23% in bile within 6 hr after oral administration of N-¹⁴CH₃- PG-501 at the dose of 12.5 mg/kg. After intravenous administration of the drug to the rat, the excretion rate was 41% in urine, 8% in feces, and 30% in the expired air during 24 hr, and 26% in bile within 6 hr.