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首页> 外文期刊>Drug Metabolism and Disposition: The Biological Fate of Chemicals >Peony-Glycyrrhiza Decoction, an Herbal Preparation, Inhibits Clozapine Metabolism via Cytochrome P450s, but Not Flavin-Containing Monooxygenase in In Vitro Models
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Peony-Glycyrrhiza Decoction, an Herbal Preparation, Inhibits Clozapine Metabolism via Cytochrome P450s, but Not Flavin-Containing Monooxygenase in In Vitro Models

机译：牡丹-甘草汤，一种中草药制剂，在体外模型中通过细胞色素P450抑制氯氮平代谢，但不含有黄素单加氧酶。

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摘要

Our previous studies have shown the therapeutic efficacy and underlying mechanisms of Peony-Glycyrrhiza Decoction (PGD), an herbal preparation, in treating antipsychotic-induced hyperprolactinemia in cultured cells, animal models, and human subjects. In the present study, we further evaluated pharmacokinetic interactions of PGD with clozapine (CLZ) in human liver microsomes (HLM), recombinantly expressed cytochrome P450s (P450s), and flavin-containing monooxygenases (FMOs). CLZ metabolites, N-demethyl-clozapine and clozapine-N-oxide, were measured. PGD, individual peony and glycyrrhiza preparations, and the two individual preparations in combination reduced production of CLZ metabolites to different extents in HLM. While the known bioactive constituents of PGD play a relatively minor role in the kinetic effects of PGD on P450 activity, PGD as a whole had a weak-to-moderate inhibitory potency toward P450s, in particular CYP1A2 and CYP3A4. FMOs are less actively involved in mediating CLZ metabolism and the PGD inhibition of CLZ. These results suggest that PGD has the capacity to suppress CLZ metabolism in the human liver microsomal system. This suppression is principally associated with the inhibition of related P450 activity but not FMOs. The present study provides in vitro evidence of herb-antipsychotic interactions.
机译：我们先前的研究表明，草药制剂牡丹甘草汤（PGD）在培养的细胞，动物模型和人类受试者中治疗抗精神病药物引起的高泌乳素血症的疗效和潜在机制。在本研究中，我们进一步评估了PGD与氯氮平（CLZ）在人肝微粒体（HLM），重组表达的细胞色素P450（P450）和含黄素的单加氧酶（FMO）中的药代动力学相互作用。测定了CLZ代谢产物N-去甲基-氯氮平和氯氮平-N-氧化物。 PGD​​，单独的牡丹和甘草制剂以及两种单独的制剂组合可在HLM中不同程度地减少CLZ代谢产物的产生。尽管PGD的已知生物活性成分在PGD对P450活性的动力学影响中起相对较小的作用，但PGD总体上对P450尤其是CYP1A2和CYP3A4的抑制作用弱到中度。 FMO较少积极参与介导CLZ代谢和PGD抑制CLZ。这些结果表明，PGD具有抑制人肝微粒体系统中CLZ代谢的能力。这种抑制作用主要与相关P450活性的抑制有关，而与FMO无关。本研究提供了草药-抗精神病药物相互作用的体外证据。

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