Jingyin Granules Modulate Pharmacokinetics of CYP Substrate-Drugs by Inactivating CYP3A

Strategic Insights -

Research conducted at the Shanghai University of Traditional Chinese Medicine has found that Jingyin granules, a marketed antiviral herbal medicine, modulate the pharmacokinetics of CYP substrate-drugs by inactivating CYP3A. This study aimed to assess the inhibitory potency of the herbal extract of Jingyin granules against human drug-metabolizing enzymes and clarify whether it can modulate the pharmacokinetic profiles of Western drug(s) in vivo. The results demonstrated that Jingyin granules dose-dependently inhibited human CES1A, CES2A, CYPs1A, 2A6, 2C8, 2C9, 2D6, and 2E1, and time- and NADPH-dependently inhibited human CYP2C19 and CYP3A. In vivo tests showed that Jingyin granules significantly increased the plasma exposure of lopinavir, a CYP3A-substrate drug, by 2.43-fold and strongly prolonged its half-life by 1.91-fold when co-administered with lopinavir to rats.

Key Takeaways:

  • Jingyin granules, a marketed antiviral herbal medicine, modulate the pharmacokinetics of CYP substrate-drugs by inactivating CYP3A.
  • The herbal extract of Jingyin granules (HEJG) dose-dependently inhibited human CES1A, CES2A, CYPs1A, 2A6, 2C8, 2C9, 2D6, and 2E1.
  • HEJG time- and NADPH-dependently inhibited human CYP2C19 and CYP3A.
  • In vivo tests showed that HEJG significantly increased the plasma exposure of lopinavir by 2.43-fold and prolonged its half-life by 1.91-fold.
  • The study revealed that licochalcone A, licochalcone B, licochalcone C, and echinatin in Radix Glycyrrhizae, as well as quercetin and kaempferol in Folium Llicis Purpureae, are time-dependent CYP3A inhibitors.

Statistics:

  • Jingyin granules increased the plasma exposure of lopinavir by 2.43-fold.
  • The half-life of lopinavir was prolonged by 1.91-fold.
  • Jingyin granules inhibited human CES1A, CES2A, CYPs1A, 2A6, 2C8, 2C9, 2D6, and 2E1 dose-dependently.
  • HEJG inhibited human CYP2C19 and CYP3A time- and NADPH-dependently.

Sources:

  • Inhibition of Drug-metabolizing Enzymes By Jingyin Granules: Implications of Herb-drug Interactions In Antiviral Therapy. Acta Pharmacologica Sinica, 2022;43(4):1072-1081.
  • Shanghai University of Traditional Chinese Medicine, Inst Interdisciplinary Integrat Med Res, Shanghai 201203, People's Republic of China.
  • Hong-zhuan Chen, Shanghai University of Traditional Chinese Medicine.