In vitro inhibitory effect of lysionotin on the activity of cytochrome P450 enzymes.

This study investigated the interaction between lysionotin and CYPs. MATERIAL AND METHOD: The effects of 100 μM lysionotin on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs) with specific inhibitor as positive control and untreated HLMs as control. Meanwhile, the enzyme kinetic parameters were calculated. A time-dependent study was performed with a time interval of 5 min in 30 min. RESULTS: Lysionotin was found to inhibit the activity of CYP3A4, 2C19, and 2C8, with IC50 values of 13.85, 24.95, and 30.05 μM, respectively. The inhibition of CYP3A4 was performed in a non-competitive manner with the Ki value of 6.83 μM, while the inhibition of CYP2C19 and 2C8 was performed in a competitive manner with Ki values of 12.41 and 14.51 μM. Moreover, it was found that the inhibition of CYP3A4 was time-dependent with K I/K inact value of 6.618/0.048 min/μM. Discussion and conclusions: The in vitro inhibitory effect of lysionotin on the activity of CYP3A4, 2C19, and 2C8 indicated potential drug interactions between lysionotin and drugs metabolised by CYP3A4, 2C19, and 2C8. Further in vivo experiments are needed to assess the potential interactions. PMID: 32673137 [PubMed - in process]
Source: Pharmaceutical Biology - Category: Drugs & Pharmacology Tags: Pharm Biol Source Type: research