Cytochrome P450 metabolic intermediate complex of nefopam

Abstract

Abstract NADPH-catalysed biotransformation of nefopam in liver microsomes obtained from phenobarbitone-pretreated rats leads to the formation of an inactive cytochrome P450 metabolic intermediate (MI) complex. This complex can be detected spectrophotometrically by an absorbance maximum at 459 nm. The extent of the in-vitro MI complexation of 33 μm nefopam, a cyclic analogue of orphenadrine, was almost equal to the extent of the in-vitro MI complexation of 33 μm tofenacine, the mono-N-demethylated metabolite of orphenadrine. The time course of the MI complexation of nefopam and studies with two of its major metabolites suggest an initial biotransformation, which has to occur before MI complexation can take place. Maximal MI complexation of nefopam occurred at approximately 25 μm, whereas the MI complexation could not be detected at 100 μm nefopam.