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Influence of methylxanthines isolated from Bancha green tea on the pharmacokinetics of sildenafil in rats

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Abstract

Background

Sildenafil is used to treat erectile dysfunction and pulmonary arterial hypertension and is metabolized in the liver mainly by CYP3A4, thus co-administration with drugs or herbal extracts that affect CYP3A4 activity may lead to drug-drug or drug-herb interactions, respectively. The aim of the present study was to evaluate the influence of single and multiple oral doses of methylxanthine fraction, isolated from Bancha green tea leaves on the pharmacokinetics of sildenafil in rats.

Methods

Rats were given sildenafil alone as well as simultaneously with methylxanthines or ketoconazole. The plasma concentrations of sildenafil were measured with high-performance liquid chromatography method with ultraviolet detection. The pharmacokinetic parameters of sildenafil were calculated by non-compartmental analysis.

Results

Concomitant use of sildenafil with a single oral dose of methylxanthines resulted in a decrease in Cmax (p > 0.05), AUC0-t (p < 0.05) and AUC0-inf (p < 0.05), while the administration of sildenafil after methylxanthines pretreatment resulted in an increase in Cmax (p < 0.0001), AUC0-t (p < 0.0001) and AUC0-inf (p < 0.001) compared to the sildenafil group. After co-administration of sildenafil and ketoconazole, a significant increase in Cmax, AUC0-t and AUC0-inf was observed in both of the experiments.

Conclusion

Drug-herb interactions were observed when sildenafil was co-administered with Bancha methylxanthines in rats. Further in vivo studies about the potential drug interactions between sildenafil and methylxanthines, especially caffeine, are needed to clarify mechanisms underlying the observed changes in sildenafil pharmacokinetics.

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Data availability

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Acknowledgments

The authors would like to thank the entire team of Science and Research Department at Medical University “Prof. Dr. Paraskev Stoyanov” for their support.

Funding

This study was funded by the Science Fund of Medical University “Prof. Dr. Paraskev Stoyanov” (project № 20019).

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Authors and Affiliations

  1. Department of Pharmacology, toxicology and pharmacotherapy, Faculty of Pharmacy, Medical University “Prof. Dr. Paraskev Stoyanov”, 84 “Tsar Osvoboditel” Blvd, 9000, Varna, Bulgaria

    Maya Radeva-llieva, Stanila Stoeva, Nadezhda Hvarchanova & Kaloyan D. Georgiev

  2. Department of Biology, Faculty of Pharmacy, Medical University “Prof. Dr. Paraskev Stoyanov”, 84 “Tsar Osvoboditel” Blvd, 9000, Varna, Bulgaria

    Iliya Zhelev

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  1. Maya Radeva-llieva
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Contributions

MRI performed the literature review and wrote the manuscript. IZ extracted Bancha methylxanthines. MRI carried out the randomization and was aware of the group allocation. MRI, NH, SS and KG conducted the experiments. SS and MRI performed the HPLC analysis. All authors contributed to the design of the study and data analysis. All authors read and approved the final version of the manuscript before submission.

Corresponding author

Correspondence to Maya Radeva-llieva.

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The authors have no financial and non-financial conflicts of interest to declare.

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The study protocol was approved by the Bulgarian Food Safety Agency and all the requirements for the protection and humane treatment of laboratory animals according to the Directive 2010/63/EU were followed.

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Radeva-llieva, M., Stoeva, S., Hvarchanova, N. et al. Influence of methylxanthines isolated from Bancha green tea on the pharmacokinetics of sildenafil in rats. DARU J Pharm Sci 30, 75–84 (2022). https://doi.org/10.1007/s40199-022-00433-z

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