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Pharmacokinetic Evaluation of Clozapine in Concomitant Use of Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, or Fructus Gardeniae in Rats
- Source :
- Molecules; Volume 21; Issue 6; Pages: 696, Molecules, Vol 21, Iss 6, p 696 (2016), Molecules
- Publication Year :
- 2016
- Publisher :
- MDPI AG, 2016.
-
Abstract
- 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.
- Subjects :
- Male
Herb-Drug Interactions
Pharmaceutical Science
Pharmacology
Kidney Function Tests
complex mixtures
030226 pharmacology & pharmacy
Article
Analytical Chemistry
lcsh:QD241-441
03 medical and health sciences
herb-drug interaction
0302 clinical medicine
Liver Function Tests
lcsh:Organic chemistry
Pharmacokinetics
Drug Discovery
medicine
Animals
Drug Interactions
Tissue Distribution
Radix
Physical and Theoretical Chemistry
Clozapine
Radix bupleuri
clozapine
Traditional medicine
medicine.diagnostic_test
business.industry
Organic Chemistry
herbal medicine
pharmacokinetics
metabolism
Rats
Chemistry (miscellaneous)
030220 oncology & carcinogenesis
Pharmacodynamics
Concomitant
Schizophrenia
Molecular Medicine
Drug Therapy, Combination
Liver functions
business
Liver function tests
Drugs, Chinese Herbal
medicine.drug
Subjects
Details
- ISSN :
- 14203049
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....3d3fb3a1bebf6c9a942642d20cfd8eaf
- Full Text :
- https://doi.org/10.3390/molecules21060696