In-vitro and in-vivo evaluations of cytochrome P450 1A2 interactions with nuciferine

Abstract Objectives The effects of nuciferine, a major active aporphine alkaloid from the leaves of Nelumbo nucifera Gaertn, on a cytochrome P450 1A2 (CYP1A2) probe substrate were investigated in vitro and in vivo. Methods Nuciferine and recombinant human CYP1A2 were incubated together to study the impact of nuciferine on CYP1A2 in vitro. Nuciferine was administered orally to Wistar rats at a dose of 20 mg/kg to further estimate the impact of nuciferine on CYP1A2 in vivo. A probe substrate, phenacetin, was used to index the activity of CYP1A2. Key findings The IC50 value for nuciferine was determined to be 2.12 mmol/l. When phenacetin was intravenously coadministered with nuciferine compared with phenacetin alone, the elimination rate constant and total body clearance of phenacetin were decreased by 24.0% (P < 0.01) and 43.0% (P < 0.05), respectively. The mean residence time, apparent elimination half-time and area under the plasma concentration–time curve were increased by 22% (P < 0.005), 26.9% (P < 0.02) and 74.6% (P < 0.05), respectively. Similarly, when phenacetin was coadministered orally with nuciferine, the apparent elimination half-time in the nuciferine pretreated group was increased by 16.7% (P < 0.05) and the elimination rate constant was decreased by 15.4% (P < 0.05). Conclusions The results suggest that nuciferine inhibited CYP1A2 activity in vitro and caused changes in the pharmacokinetic parameters of phenacetin in vivo.