Effects of Baicalin on Oral Pharmacokinetics of Caffeine in Rats

Noh, Keumhan; Nepal, Mahesh Raj; Jeong, Ki Sun; Kim, Sun A.; Um, Yeon Ji; Seo, Chae Shin; Kang, Mi Jeong; Park, Pil Hoon; Kang, Wonku; Jeong, Hye Gwang; Jeong, Tae Cheon

doi:10.4062/biomolther.2014.134

Cited by 19 publications

(13 citation statements)

References 20 publications

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“…First, we optimized the liquid chromatography to achieve good chromatographic separation among the isomers, caffeine, and their internal standards. Secondly, we addressed the importance of HCOOH on signal intensity and matrix effects of the analytes, which has been largely ignored by the earlier reported assays (Choi, Bae, Park, Kwon, Jang, Zheng, Lee, Lee and Bae 2013, Noh, Nepal, Jeong, Kim, Um, Seo, Kang, Park, Kang, Jeong and Jeong 2015, Noh, Oh, Nepal, Jeong, Choi, Kang, Kang, Jeong and Jeong 2016). Thirdly, we utilized isotopic analogs as internal standards ( i.e ., CAF-d9 for CAF, PAR-d3 for PAR, THY, and THM).…”

Section: Resultsmentioning

confidence: 99%

Measurement of caffeine and its three primary metabolites in human plasma by HPLC‐ESI‐MS/MS and clinical application

Chen

Parker

et al. 2017

Biomedical Chromatography

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Caffeine is a mild stimulant with significant potential for abuse being consumed in larger doses with the widespread availability of energy drinks and by novel routes of administration such as inspired powder, oral sprays, and electronic cigarettes. How these recent changes in caffeine consumption affecting caffeine disposition and abuse potential is of growing concern. In the study of caffeine disposition in humans, it is common to only measure the caffeine concentration; however, caffeine’s three major metabolites (paraxanthine, theobromine, and theophylline) retain central nervous system stimulant activity that may contribute to the overall pharmacological activity and toxicity. Therefore, it would be scientifically more rigorous to measure caffeine and its major metabolites in the evaluation of caffeine disposition in human subjects. Herein, we report a method for the simultaneous quantification of caffeine and its three major metabolites in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry (HPLC-ESI-MS/MS). Human plasma samples were treated by simple protein precipitation and the analytes were separated using a 6-min gradient program. Precision and accuracy were well within in the 15% acceptance range. The simple sample preparation, short runtime, sensitivity, and the inclusion of caffeine’s major metabolites make this assay methodology optimal for the study of caffeine’s pharmacokinetics and pharmacodynamics in human subjects.

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Section: Resultsmentioning

confidence: 99%

Measurement of caffeine and its three primary metabolites in human plasma by HPLC‐ESI‐MS/MS and clinical application

Chen

Parker

et al. 2017

Biomedical Chromatography

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“…The results indicated that CYP 1A would be selectively inhibited by chrysin in vitro . Thereby, the effect of chrysin on caffeine pharmacokinetics were studied in vivo because caffeine is a well-known substrate for CYP 1A (Noh et al ., 2015). …”

Section: Resultsmentioning

confidence: 99%

“…By enrichment, the inhibitory effects of chrysin on specific CYP isozymes could be more selectively determined (Noh et al ., 2015). Dexamethasone and 3-methylcholanthrene suspended in corn oil were intraperitoneally given to rats at a dose of 50 mg/kg and 40 mg/kg for 3 consecutive days, respectively.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic Interaction of Chrysin with Caffeine in Rats

Noh

Nepal

et al. 2016

Biomolecules & Therapeutics

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Pharmacokinetic interaction of chrysin, a flavone present in honey, propolis and herbs, with caffeine was investigated in male Sprague-Dawley rats. Because chrysin inhibited CYP1A-selective ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase activities in enriched rat liver microsomes, the pharmacokinetics of caffeine, a CYP 1A substrate, was studied following an intragastric administration with 100 mg/kg chrysin. In addition to the oral bioavailability of chrysin, its phase 2 metabolites, chrysin sulfate and chrysin glucuronide, were determined in rat plasma. As results, the pharmacokinetic parameters for caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) were not changed following chrysin treatment in vivo, despite of its inhibitory effect on CYP 1A in vitro. The bioavailability of chrysin was found to be almost zero, because chrysin was rapidly metabolized to its sulfate and glucuronide conjugates in rats. Taken together, it was concluded that the little interaction of chrysin with caffeine might be resulted from the rapid metabolism of chrysin to its phase 2 metabolites which would not have inhibitory effects on CYP enzymes responsible for caffeine metabolism.

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“…Meanwhile, Noh et al . [40] reported that, although baicalin inhibited CYP1A activity in rat liver microsomes in vitro , there was no difference between pharmacokinetics of caffeine and its metabolites ( i.e. , paraxanthine, theobromine, and theophylline), when caffeine was orally administered 8 h after single intragastric administration with baicalin (0.2 g/kg) in rats, because sufficient plasma concentration of baicalin for CYP inhibition could not be reached.…”

Section: Baicalin and Baicalein Induced In Vivo Drug Interactionmentioning

confidence: 99%

Role of Intestinal Microbiota in Baicalin-Induced Drug Interaction and Its Pharmacokinetics

et al. 2016

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Since many glycoside compounds in natural products are hydrolyzed by intestinal microbiota when administered orally, it is of interest to know whether their pharmacological effects are derived from the glycoside itself or from the aglycone form in vivo. An interesting example is baicalin versus baicalein, the aglycone of baicalin, which is contained in some herbs from Labiatae including Scutellaria baicalensis Georgi and Scutellaria lateriflora Linne. The herbs have been extensively used for treatment of inflammatory diseases in Asia. Although there have been numerous reports regarding the pharmacological effects of baicalin and baicalein in vivo and in vitro, some reports indicated that the glycoside form would hardly be absorbed in the intestine and that it should be hydrolyzed to baicalein in advance for absorption. Therefore, the role of metabolism by intestinal microbiota should also be considered in the metabolism of baicalin. In addition, baicalin contains a glucuronide moiety in its structure, by which baicalin and baicalein show complex pharmacokinetic behaviors, due to the interconversion between them by phase II enzymes in the body. Recently, concerns about drug interaction with baicalin and/or baicalein have been raised, because of the co-administration of Scutellaria species with certain drugs. Herein, we reviewed the role of intestinal microbiota in pharmacokinetic characteristics of baicalin and baicalein, with regards to their pharmacological and toxicological effects.

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Effects of Baicalin on Oral Pharmacokinetics of Caffeine in Rats

Cited by 19 publications

References 20 publications

Measurement of caffeine and its three primary metabolites in human plasma by HPLC‐ESI‐MS/MS and clinical application

Measurement of caffeine and its three primary metabolites in human plasma by HPLC‐ESI‐MS/MS and clinical application

Pharmacokinetic Interaction of Chrysin with Caffeine in Rats

Role of Intestinal Microbiota in Baicalin-Induced Drug Interaction and Its Pharmacokinetics

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