Hydrastine Pharmacokinetics and Metabolism after a Single Oral Dose of Goldenseal (Hydrastis canadensis) to Humans
| Autor: | Prem K. Gupta, Howard P. Hendrickson, Gary W. Barone, E. Kim Fifer, Bill J. Gurley |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Hydrastis Cmax Administration Oral Pharmaceutical Science Pilot Projects Urine Tandem mass spectrometry Benzylisoquinolines Hydroxylation chemistry.chemical_compound Drug Stability Pharmacokinetics Tandem Mass Spectrometry medicine Humans Tissue Distribution Goldenseal Pharmacology Chromatography biology biology.organism_classification Healthy Volunteers Metabolic Detoxication Phase II Hydrastine chemistry Dietary Supplements Female Metabolic Detoxication Phase I Glucuronide Chromatography Liquid medicine.drug |
| Zdroj: | Drug Metabolism and Disposition. 43:534-552 |
| ISSN: | 1521-009X 0090-9556 |
| DOI: | 10.1124/dmd.114.059410 |
| Popis: | The disposition and metabolism of hydrastine was investigated in 11 healthy subjects following an oral dose of 2.7 g of goldenseal supplement containing 78 mg of hydrastine. Serial blood samples were collected for 48 hours, and urine was collected for 24 hours. Hydrastine serum and urine concentrations were determined by Liquid Chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters for hydrastine were calculated using noncompartmental methods. The maximal serum concentration (Cmax) was 225 ± 100 ng/ml, Tmax was 1.5 ± 0.3 hours, and area under the curve was 6.4 ± 4.1 ng ⋅ h/ml ⋅ kg. The elimination half-life was 4.8 ± 1.4 hours. Metabolites of hydrastine were identified in serum and urine by using liquid chromatography coupled to high-resolution mass spectrometry. Hydrastine metabolites were identified by various mass spectrometric techniques, such as accurate mass measurement, neutral loss scanning, and product ion scanning using Quadrupole-Time of Flight (Q-ToF) and triple quadrupole instruments. The identity of phase II metabolites was further confirmed by hydrolysis of glucuronide and sulfate conjugates using bovine β-glucuronidase and a Helix pomatia sulfatase/glucuronidase enzyme preparation. Hydrastine was found to undergo rapid and extensive phase I and phase II metabolism. Reduction, O-demethylation, N-demethylation, hydroxylation, aromatization, lactone hydrolysis, and dehydrogenation of the alcohol group formed by lactone hydrolysis to the ketone group were observed during phase I biotransformation of hydrastine. Phase II metabolites were primarily glucuronide and sulfate conjugates. Hydrastine undergoes extensive biotransformation, and some metabolites may have pharmacological activity. Further study is needed in this area. |
| Databáze: | OpenAIRE |
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