Pharmacokinetics of haloalkylamines: cyclization and distribution in blood in vitro and in vivo

The cyclization of N-(5-chloropentyl)-N-methylaminoaceto-2,6-xylidide hydrochloride (RAD 150) and N-(5-bromopentyl)-N-methylamino-aceto-2,6-xylide hydrobromide (RAD 154) in red blood cells of rats and rabbits was examined under in vitro and in vivo conditions. The rate of cyclization was much slower in plasma and blood than in a buffer solution, probably due to influence of protein binding of the compounds. The tertiary amines disappeared rapidly from the blood cells in vitro and in vivo and the piperidinium derivative (RAD 179) formed from the haloalkylamines disappeared almost as rapidly as the tertiary amines from the plasma in vivo. In contrast, the efflux of RAD 179 formed in the blood cells was slow (T 1/2 for rabbit erythrocytes: 9 h in vitro; 8 h in vivo) following a 1st order reaction. RAD 179 itself was only to a small extent taken up in the blood cells.