Abstract
Corona Virus Disease 2019 (COVID-19) has spread all over the world and brings significantly negative effects on human health. To fight against COVID-19 in a more efficient way, drug-drug or drug-herb combinations are frequently used in clinical settings. The concomitant use of multiple medications may trigger clinically relevant drug/herb-drug interactions. This study aims to assay the inhibitory potentials of Qingfei Paidu decoction (QPD, a Chinese medicine compound formula recommended for combating COVID-19 in China) against human drug-metabolizing enzymes and to assess the pharmacokinetic interactions in vivo. The results demonstrated that QPD dose-dependently inhibited CYPs1A, 2A6, 2C8, 2C9, 2C19, 2D6 and 2E1 but inhibited CYP3A in a time- and NADPH-dependent manner. In vivo test showed that QPD prolonged the half-life of lopinavir (a CYP3A substrate-drug) by 1.40-fold and increased the AUC of lopinavir by 2.04-fold, when QPD (6 g/kg) was co-administrated with lopinavir (160 mg/kg) to rats. Further investigation revealed that Fructus Aurantii Immaturus (Zhishi) in QPD caused significant loss of CYP3A activity in NADPH-generating system. Collectively, our findings revealed that QPD potently inactivated CYP3A and significantly modulated the pharmacokinetics of CYP3A substrate-drugs, which would be very helpful for the patients and clinicians to avoid potential drug-interaction risks in COVID-19 treatment.
Keywords: CYP3A substrate-drugs; Cytochrome P450 enzymes (CYPs/P450s); Herb-drug interactions (HDIs); Qingfei Paidu decoction (QPD).
【저자키워드】 CYP3A substrate-drugs, Cytochrome P450 enzymes (CYPs/P450s), Herb-drug interactions (HDIs), Qingfei Paidu decoction (QPD)., 【초록키워드】 COVID-19, Treatment, Lopinavir, risk, pharmacokinetics, COVID-19 treatment, Spread, China, Health, Corona, medication, in vivo, interactions, inactivated, half-life, pharmacokinetic, Combination, Interaction, Trigger, AUC, Virus Disease, cytochrome P450, Herb, clinician, enzyme, RATs, clinical settings, Chinese, concomitant use, Cytochrome P450 enzymes, NADPH, P450s, inhibitory, Effect, combating, caused, significantly, the patient, clinically, inhibited, demonstrated, modulated, 【제목키워드】 COVID-19, inhibition, Interaction, enzyme,