The reversibility of N-oxidation in vivo : The fate of 14C- N-hydroxychlorphentermine and 14C-nitrochlorphentermine in the rat

Abstract

The interrelationships between primary amines and their in vivo N-oxidized metabolites are unclear. We have therefore synthesized 14C- N-hydroxychlorphentermine and 14C-nitrochlorphentermine and examined their metabolism and excretion in the rat. 14C- N-hydroxychlorphentermine was excreted slowly in the urine (66 per cent of dose in 6 days) with a further 8 per cent in the faeces (3 per cent) and as 14CO 2 (5 per cent), and the only urinary metabolites were the unchanged hydroxylamine and its glucuronic acid conjugate. 14C-Nitrochlorphentermine was eliminated more rapidly (92 per cent of dose in 4 days), with 41 per cent in the urine, 1 per cent in the faeces and 50 per cent as 14CO 2. The only urinary metabolites were the reduction product N-hydroxychlorphentermine and its glucuronide but the large amount of 14CO 2 found indicated that side chain oxidation was a major metabolic route. The results are discussed with reference to the possible reversibility of N-oxidation in vivo and putative mechanisms for the oxidation of the side chain.