Herb–drug interaction studies of ethanolic extract of Cassia occidentalis L. coadministered with acetaminophen, theophylline, omeprazole, methotrexate and methylprednisolone

Abstract

Background: Traditionally Cassia occidentalis L. extract is used for the treatment of several diseases including fever, bone diseases, fracture, kidney and digestive diseases. Ethanolic extract of Cassia occidentalis L. (EECO) is being developed as a phytopharmaceutical for corticosteroid-induced osteoporosis. Purpose: This study was aimed to investigate the effect of EECO on the pharmacokinetics of acetaminophen (ACET), theophylline (THEO), omeprazole (OMEP), methotrexate (MTX), and methylprednisolone (MP). Methods: Interaction studies were performed in Sprague Dawley (SD) rats. ACET (100 mg/kg), THEO (25 mg/kg), OMEP (40 mg/kg), MTX (5 mg/kg), or MP (5 mg/kg) was administered with and without EECO (250 mg/kg) separately. Results: The LLOQ of all analytes was 10 ng/mL except for OMEP (1 ng/mL) and r2 > 0.994. The intra-day and inter-day RSD (%) were ≤12.13 and accuracy (%) was between 89.19 and 112.67 at four QC levels. Our results suggested that EECO caused interaction when coadministered with ACET, MTX and MP. No changes were found in the bioavailability of THEO and OMEP. EECO had inhibitory effects on CYP1A2, CYP2C9 and CYP3A4. Conclusions: Based on these results, dose adjustment may be required when ACET, MP and MTX are coadministered with EECO. These results would be useful for phase 1 clinical trial of EECO.

Keywords

• Cassia occidentalis
• Herb–drug interactions
• Acetaminophen
• Theophylline
• Methotrexate
• Methylprednisolone