Abstract
Context: Triptolide and amlodipine are often simultaneously used for reducing urine protein excretion after renal transplantation in China clinics.Objective: This study investigated the effects of triptolide on the pharmacokinetics of amlodipine in male Sprague–Dawley rats.Materials and methods: The pharmacokinetics of amlodipine (1 mg/kg) with or without triptolide pre-treatment (2 mg/kg/day for seven days) were investigated using a sensitive and reliable LC–MS/MS method. Additionally, the inhibitory effects of triptolide on the metabolic stability of amlodipine were investigated using rat liver microsome incubation systems.Results: The results indicated that when the rats were pre-treated with triptolide, the Cmax of amlodipine increased from 13.78 ± 3.57 to 19.96 ± 4.56 ng/mL (p < 0.05), the Tmax increased from 4.04 ± 1.15 to 5.89 ± 1.64 h (p < 0.05), and the AUC0–t increased by approximately 104% (p < 0.05), which suggested that the pharmacokinetic behaviour of amlodipine was affected after oral co-administration of triptolide. Additionally, the metabolic half-life was prolonged from 22.5 ± 4.26 to 36.8 ± 6.37 min (p < 0.05) with the pre-treatment of triptolide.Conclusions: In conclusion, these results indicated that triptolide could affect the pharmacokinetics of amlodipine, possibly by inhibiting the metabolism of amlodipine in rat liver when they are co-administered.
Highlights
Amlodipine is a dihydropyridine calcium-channel blocker widely used for the treatment of hypertension and ischemic heart disease in clinic (Hotha et al 2013; Adake et al 2015; Agrawal et al 2015; Feldman et al 2016)
Triptolide and amlodipine are often simultaneously used for reducing urine protein excretion after renal transplantation in Chinese clinics
This study develops a sensitive and reliable LC–MS/MS method for the determination of amlodipine in rat plasma, compares the pharmacokinetics of amlodipine after oral administration of single amlodipine or both triptolide and amlodipine, investigates the inhibitory effects of triptolide on the metabolic stability of amlodipine, and provides a guide for clinical medication of triptolide and amlodipine to avoid the occurrence of adverse reactions
Summary
Amlodipine is a dihydropyridine calcium-channel blocker widely used for the treatment of hypertension and ischemic heart disease in clinic (Hotha et al 2013; Adake et al 2015; Agrawal et al 2015; Feldman et al 2016). Drugs which inhibit the activity of CYP3A4 might affect the pharmacokinetic profiles of amlodipine when they are co-administered (Hsiao et al 2015; Zheng et al 2016). Triptolide and amlodipine are often simultaneously used for reducing urine protein excretion after renal transplantation in Chinese clinics. It is unknown whether triptolide could affect the pharmacokinetics of amlodipine. A better understanding of the pharmacokinetic interaction between triptolide and amlodipine would help link data from pharmacological assays to clinical effects, facilitating the design of rational dosage regimens and avoiding the occurrence of adverse reactions (Yang et al 2006, 2011; Park et al 2017)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
