In vitro results suggest that Physeptone undergoes hepatic N-demethylation by cytochrome P450 enzymes, principally CYP3A4, CYP2B6, CYP2C19 and to a lesser extent by CYP2C9 and CYP2D6. Coadministration of Physeptone with CYP inducers of these enzymes may result in a more rapid metabolism and potential for decreased effects of Physeptone, whereas administration with CYP inhibitors may reduce metabolism and potentiate methadones effects. Although antiretroviral drugs such as efavirenz, nelfinavir, nevirapine, ritonavir, lopinavir+ritonavir combination are known to inhibit CYPs, they are shown to reduce the plasma levels of Physeptone, possibly due to their CYP induction activity. Therefore, drugs administered concomitantly with Physeptone should be evaluated for interaction potential; clinicians are advised to evaluate individual response to drug therapy.
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