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Time effect of rutaecarpine on caffeine pharmacokinetics in rats

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. Thi...

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Detalles Bibliográficos
Autores principales: Estari, Rohit Kumar, Dong, Jin, Chan, William K., Park, Miki Susanto, Zhou, Zhu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429912/
https://www.ncbi.nlm.nih.gov/pubmed/34527815
http://dx.doi.org/10.1016/j.bbrep.2021.101121
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author Estari, Rohit Kumar
Dong, Jin
Chan, William K.
Park, Miki Susanto
Zhou, Zhu
author_facet Estari, Rohit Kumar
Dong, Jin
Chan, William K.
Park, Miki Susanto
Zhou, Zhu
author_sort Estari, Rohit Kumar
collection PubMed
description 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.
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spelling pubmed-84299122021-09-14 Time effect of rutaecarpine on caffeine pharmacokinetics in rats Estari, Rohit Kumar Dong, Jin Chan, William K. Park, Miki Susanto Zhou, Zhu Biochem Biophys Rep Research Article 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. Elsevier 2021-09-06 /pmc/articles/PMC8429912/ /pubmed/34527815 http://dx.doi.org/10.1016/j.bbrep.2021.101121 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Estari, Rohit Kumar
Dong, Jin
Chan, William K.
Park, Miki Susanto
Zhou, Zhu
Time effect of rutaecarpine on caffeine pharmacokinetics in rats
title Time effect of rutaecarpine on caffeine pharmacokinetics in rats
title_full Time effect of rutaecarpine on caffeine pharmacokinetics in rats
title_fullStr Time effect of rutaecarpine on caffeine pharmacokinetics in rats
title_full_unstemmed Time effect of rutaecarpine on caffeine pharmacokinetics in rats
title_short Time effect of rutaecarpine on caffeine pharmacokinetics in rats
title_sort time effect of rutaecarpine on caffeine pharmacokinetics in rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429912/
https://www.ncbi.nlm.nih.gov/pubmed/34527815
http://dx.doi.org/10.1016/j.bbrep.2021.101121
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