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Article: Peony-Glycyrrhiza Decoction, an herbal preparation, inhibits clozapine metabolism via cytochrome P450s, but not flavin-containing monooxygenase in in vitro models

TitlePeony-Glycyrrhiza Decoction, an herbal preparation, inhibits clozapine metabolism via cytochrome P450s, but not flavin-containing monooxygenase in in vitro models
Authors
Issue Date2015
PublisherAmerican Society for Pharmacology and Experimental Therapeutics.
Citation
Drug Metabolism and Disposition, 2015, v. 43 n. 7, p. 1147-1153 How to Cite?
AbstractOur 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.
Persistent Identifierhttp://hdl.handle.net/10722/215631
ISSN
2015 Impact Factor: 3.21
2015 SCImago Journal Rankings: 1.249

 

DC FieldValueLanguage
dc.contributor.authorWang, W-
dc.contributor.authorTian, DD-
dc.contributor.authorZheng, B-
dc.contributor.authorWang, D-
dc.contributor.authorTan, QR-
dc.contributor.authorWang, CY-
dc.contributor.authorZhang, Z-
dc.date.accessioned2015-08-21T13:33:26Z-
dc.date.available2015-08-21T13:33:26Z-
dc.date.issued2015-
dc.identifier.citationDrug Metabolism and Disposition, 2015, v. 43 n. 7, p. 1147-1153-
dc.identifier.issn0090-9556-
dc.identifier.urihttp://hdl.handle.net/10722/215631-
dc.description.abstractOur 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.-
dc.languageeng-
dc.publisherAmerican Society for Pharmacology and Experimental Therapeutics. -
dc.relation.ispartofDrug Metabolism and Disposition-
dc.titlePeony-Glycyrrhiza Decoction, an herbal preparation, inhibits clozapine metabolism via cytochrome P450s, but not flavin-containing monooxygenase in in vitro models-
dc.typeArticle-
dc.identifier.emailTian, DD: tiandd@hku.hk-
dc.identifier.emailZhang, Z: zhangzj@hkucc.hku.hk-
dc.identifier.authorityZhang, Z=rp01297-
dc.identifier.doi10.1124/dmd.114.062653-
dc.identifier.pmid25948710-
dc.identifier.hkuros246028-
dc.identifier.volume43-
dc.identifier.issue7-
dc.identifier.spage1147-
dc.identifier.epage1153-
dc.publisher.placeUnited States-

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