Inhibition of drug-metabolizing enzymes by Qingfei Paidu decoction: Implication of herb-drug interactions in COVID-19 pharmacotherapy.
Food Chem Toxicol
; 149: 111998, 2021 Mar.
Article
em En
| MEDLINE
| ID: mdl-33476691
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.
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Texto completo:
1
Base de dados:
MEDLINE
Medicinas Tradicionais:
Medicinas_tradicionales_de_asia
/
Medicina_china
Métodos Terapêuticos e Terapias MTCI:
Terapias_biologicas
Assunto principal:
Medicamentos de Ervas Chinesas
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Interações Ervas-Drogas
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Citocromo P-450 CYP3A
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Tratamento Farmacológico da COVID-19
Tipo de estudo:
Prognostic_studies
País/Região como assunto:
Asia
Idioma:
En
Revista:
Food Chem Toxicol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China