Jornal de Metabolismo e Toxicologia de Drogas
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Comparative in-vitro Intrinsic Clearance of Imipramine in Multiple Species Liver Microsomes: Human, Rat, Mouse and Dog

Jitendra Kumar Singh, Anant Solanki and Vikas S. Shirsath

Imipramine is a renowned tricyclic anti-depressant molecule. It is known to be highly potent and efficient as compared to any other antidepressants available. There are numerous literature reports which elucidate the metabolic pathways of Imipramine. There are also various reports showing the effect of substrate and time on metabolism of Imipramine. Most of analytical methods used in these studies were of HPLC and /or of LC-MS. These studies have also been extended to identification of specific isoforms of cytochrome P450 family responsible for the metabolism of Imipramine as is outlined. Further, LC-MS based studies have also been reported on the metabolism of Imipramine in in-vitro systems including human liver microsomes and its extrapolation on human oral bioavailability data. However, till date, there has been no published report on the systematic metabolic stability of this molecule in pooled mouse and dog liver microsomes. The present study was undertaken with the aim to understand the metabolic stability of imipramine in liver microsomes of different species including human, wistar rat, CD1 mouse and male beagle dog. We have also attempted to outline the differences between the metabolic stability in these four species. The reaction samples were scanned for specific m/z values corresponding to reported metabolites, which in turn confirms microsomal metabolism.