Pharmacokinetic Evaluation of Clozapine in Concomitant Use of Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, or Fructus Gardeniae in Rats
Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, and Fructus Gardeniae are often used alongside with clozapine (CLZ) for schizophrenia patients in order to reduce side effects and enhance therapeutic efficacy. However, worse outcomes were observed raising concern about a critical issue, herb-d...
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| Format: | Article |
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MDPI AG
2016-05-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/21/6/696 |
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| author | Dan-Dan Tian Wei Wang Hua-Ning Wang Stephen Cho Wing Sze Zhang-Jin Zhang |
| author_facet | Dan-Dan Tian Wei Wang Hua-Ning Wang Stephen Cho Wing Sze Zhang-Jin Zhang |
| author_sort | Dan-Dan Tian |
| collection | DOAJ |
| description | Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, and Fructus Gardeniae are often used alongside with clozapine (CLZ) for schizophrenia patients in order to reduce side effects and enhance therapeutic efficacy. However, worse outcomes were observed raising concern about a critical issue, herb-drug interactions, which were rarely reported when antipsychotics were included. This study aims to determine whether the concomitant use of these herbal medicines affects the pharmacokinetic characteristics of CLZ in rat models. Rats were given a single or multiple intraperitoneal injections of 10 mg/kg CLZ, either alone or with individual herbal water extracts administered orally. CLZ and its two inactive metabolites, norclozapine and clozapine N-oxide, were determined by high-performance liquid chromatography/tandem mass spectrometry. In the acute treatment, the formation of both metabolites was reduced, while no significant change was observed in the CLZ pharmacokinetics for any of the herbal extracts. In the chronic treatment, none of the four herbal extracts significantly influenced the pharmacokinetic parameters of CLZ and its metabolites. Renal and liver functions stayed normal after the 11-day combined use of herbal medicines. Overall, the four herbs had limited interaction effect on CLZ pharmacokinetics in the acute and chronic treatment. Herb-drug interaction includes both pharmacokinetic and pharmacodynamic mechanisms. This result gives us a hint that pharmacodynamic herb-drug interaction, instead of pharmacokinetic types, may exist and need further confirmation. |
| first_indexed | 2024-12-11T09:04:43Z |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-11T09:04:43Z |
| publishDate | 2016-05-01 |
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| spelling | doaj.art-ac80339185124e0a826c8848da87c23f2022-12-22T01:13:40ZengMDPI AGMolecules1420-30492016-05-0121669610.3390/molecules21060696molecules21060696Pharmacokinetic Evaluation of Clozapine in Concomitant Use of Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, or Fructus Gardeniae in RatsDan-Dan Tian0Wei Wang1Hua-Ning Wang2Stephen Cho Wing Sze3Zhang-Jin Zhang4School of Chinese Medicine, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong, ChinaSchool of Chinese Medicine, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong, ChinaDepartment of Psychiatry, the fourth Military Medical University, Xi’an 710032, Shaanxi, ChinaSchool of Chinese Medicine, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong, ChinaSchool of Chinese Medicine, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong, ChinaRadix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, and Fructus Gardeniae are often used alongside with clozapine (CLZ) for schizophrenia patients in order to reduce side effects and enhance therapeutic efficacy. However, worse outcomes were observed raising concern about a critical issue, herb-drug interactions, which were rarely reported when antipsychotics were included. This study aims to determine whether the concomitant use of these herbal medicines affects the pharmacokinetic characteristics of CLZ in rat models. Rats were given a single or multiple intraperitoneal injections of 10 mg/kg CLZ, either alone or with individual herbal water extracts administered orally. CLZ and its two inactive metabolites, norclozapine and clozapine N-oxide, were determined by high-performance liquid chromatography/tandem mass spectrometry. In the acute treatment, the formation of both metabolites was reduced, while no significant change was observed in the CLZ pharmacokinetics for any of the herbal extracts. In the chronic treatment, none of the four herbal extracts significantly influenced the pharmacokinetic parameters of CLZ and its metabolites. Renal and liver functions stayed normal after the 11-day combined use of herbal medicines. Overall, the four herbs had limited interaction effect on CLZ pharmacokinetics in the acute and chronic treatment. Herb-drug interaction includes both pharmacokinetic and pharmacodynamic mechanisms. This result gives us a hint that pharmacodynamic herb-drug interaction, instead of pharmacokinetic types, may exist and need further confirmation.http://www.mdpi.com/1420-3049/21/6/696herbal medicineclozapinepharmacokineticsherb-drug interactionmetabolism |
| spellingShingle | Dan-Dan Tian Wei Wang Hua-Ning Wang Stephen Cho Wing Sze Zhang-Jin Zhang Pharmacokinetic Evaluation of Clozapine in Concomitant Use of Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, or Fructus Gardeniae in Rats Molecules herbal medicine clozapine pharmacokinetics herb-drug interaction metabolism |
| title | Pharmacokinetic Evaluation of Clozapine in Concomitant Use of Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, or Fructus Gardeniae in Rats |
| title_full | Pharmacokinetic Evaluation of Clozapine in Concomitant Use of Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, or Fructus Gardeniae in Rats |
| title_fullStr | Pharmacokinetic Evaluation of Clozapine in Concomitant Use of Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, or Fructus Gardeniae in Rats |
| title_full_unstemmed | Pharmacokinetic Evaluation of Clozapine in Concomitant Use of Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, or Fructus Gardeniae in Rats |
| title_short | Pharmacokinetic Evaluation of Clozapine in Concomitant Use of Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, or Fructus Gardeniae in Rats |
| title_sort | pharmacokinetic evaluation of clozapine in concomitant use of radix rehmanniae fructus schisandrae radix bupleuri or fructus gardeniae in rats |
| topic | herbal medicine clozapine pharmacokinetics herb-drug interaction metabolism |
| url | http://www.mdpi.com/1420-3049/21/6/696 |
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