The absorption, metabolism and excretion of (14C)-AR-L 115 BS in the baboon.

: (14C)-Labelled 2-[(2-methoxy-4-methylsulfinyl)phenyl]-1H-imidazo[4,5-b]pyridine (AR-L 115 BS) (base) was administered to male baboons by the p.o. (10 mg . kg-1 by capsule) and i.v. (2 mg.kg-1) routes. Comparison of routes and extent of excretion suggests the importance of biliary elimination and indicates that an oral dose of (14C)-AR-L 115 BS is almost quantitatively absorbed. Thus in 5 days, after the oral dose, a mean of 42% was excreted in the urine and 38% in faeces. Similarly in 0--5 days after the i.v. dose, a mean of 49% was excreted in urine and 31% in faeces. Substantial elimination of administered radioactivity was observed in the 0--24 h period: 52% following p.o. administration and 60% following i.v. administration. Plasma levels of total radioactivity peaked at 6 micrograms equiv.ml-1 4 h following an oral dose. The concentration of unchanged AR-L 115 BS at this time was ca. 4 micrograms . ml-1. 4 h following the lower i.v. dose, plasma concentrations of ca. 0.5 micrograms equiv.ml-1 were observed and were associated with ca. 0.2 micrograms . ml-1 unchanged drug. Two phases of elimination of total radioactivity from plasma after the i.v. dose could be distinguished with t1/2 ca. 2 h and ca. 48 h. An estimated late phase t1/2 of 48 h was also observed following the oral dose. Although less polar metabolites (chromatographically identical to the synthetic compounds AR-L 114 Cl (hydrochloride) and AR-L 113 Cl) were observed in the plasma at 4 h, the urine and faeces contained some polar metabolites which appeared to be neither glucuronide nor sulphate conjugates. The lower i.v. dose was apparently more extensively metabolised than the higher oral dose.