Time effect of rutaecarpine on caffeine pharmacokinetics in rats
| Autor: | William K. Chan, Rohit Kumar Estari, Zhu Zhou, Miki S. Park, Jin Dong |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Time effect
QH301-705.5 CYP1A2 Biophysics BCA Bicinchoninic acid QD415-436 Pharmacology Rutaecarpine Biochemistry pharmacokinetics PK chemistry.chemical_compound AHR aryl hydrocarbon receptor Pharmacokinetics Caffeine Biology (General) Paraxanthine GI gastrointestinal tract Potent inducer Time-dependent induction Bioavailability chemistry CYP cytochrome P450 intravenous IV Rat MROD 7-methoxyresorufin O-demethylation ANOVA Analysis of variance Research Article |
| Zdroj: | Biochemistry and Biophysics Reports, Vol 28, Iss, Pp 101121-(2021) Biochemistry and Biophysics Reports |
| ISSN: | 2405-5808 |
| Popis: | Rutaecarpine is reported as a potent inducer of CYP1A2 enzyme in rats. There are natural herbal supplements containing rutaecarpine that are designed to enhance the CYP1A2-dependent removal of caffeine from blood so that people can have coffee later in the day without causing sleep interference. This study aimed to determine the minimum amount of time needed from oral rutaecarpine administration until the observed effect of rutaecarpine on caffeine pharmacokinetics (PK) in 15 male Sprague-Dawley rats. PK parameters for caffeine and its metabolites in the control and rutaecarpine groups were calculated using WinNonlin®. Results showed that orally administered rutaecarpine at 100 mg/kg dose as early as 3 h before oral caffeine administration significantly decreased the oral systemic exposure and mean residence time of caffeine and its metabolites due to decreased caffeine bioavailability (by up to 75%) and increased clearance. The systemic exposure of caffeine and its metabolites were also decreased when caffeine was given intravenously, though this effect was less pronounced than when caffeine was given orally. Although plasma level of rutaecarpine was undetectable (less than 10 ng/mL), rutaecarpine still induced hepatic CYP1A2 activity. Results from 7-methoxyresorufin O-demethylation activity, which is specific to CYP1A2, showed that 3 h after one rutaecarpine oral dose, CYP1A2 activity in rat liver tissue was increased by 3- fold. This finding suggested that rutaecarpine effectively induced CYP1A2 activity in the liver. Highlights • Rutaecarpine significantly decreases caffeine exposure as early as 3 h. • Rutaecarpine markedly decreases caffeine metabolites exposure as early as 3 h. • Rutaecarpine decreases the oral bioavailability of caffeine by up to 75% in rats; . |
| Databáze: | OpenAIRE |
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