{"title":"板茶中甲基黄嘌呤对西地那非在大鼠体内药动学的影响。","authors":"Maya Radeva-Llieva, Stanila Stoeva, Nadezhda Hvarchanova, Iliya Zhelev, Kaloyan D Georgiev","doi":"10.1007/s40199-022-00433-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Concomitant use of sildenafil with a single oral dose of methylxanthines resulted in a decrease in C<sub>max</sub> (p > 0.05), AUC<sub>0-t</sub> (p < 0.05) and AUC<sub>0-inf</sub> (p < 0.05), while the administration of sildenafil after methylxanthines pretreatment resulted in an increase in C<sub>max</sub> (p < 0.0001), AUC<sub>0-t</sub> (p < 0.0001) and AUC<sub>0-inf</sub> (p < 0.001) compared to the sildenafil group. After co-administration of sildenafil and ketoconazole, a significant increase in C<sub>max</sub>, AUC<sub>0-t</sub> and AUC<sub>0-inf</sub> was observed in both of the experiments.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10961,"journal":{"name":"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences","volume":"30 1","pages":"75-84"},"PeriodicalIF":0.0000,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114228/pdf/40199_2022_Article_433.pdf","citationCount":"0","resultStr":"{\"title\":\"Influence of methylxanthines isolated from Bancha green tea on the pharmacokinetics of sildenafil in rats.\",\"authors\":\"Maya Radeva-Llieva, Stanila Stoeva, Nadezhda Hvarchanova, Iliya Zhelev, Kaloyan D Georgiev\",\"doi\":\"10.1007/s40199-022-00433-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Concomitant use of sildenafil with a single oral dose of methylxanthines resulted in a decrease in C<sub>max</sub> (p > 0.05), AUC<sub>0-t</sub> (p < 0.05) and AUC<sub>0-inf</sub> (p < 0.05), while the administration of sildenafil after methylxanthines pretreatment resulted in an increase in C<sub>max</sub> (p < 0.0001), AUC<sub>0-t</sub> (p < 0.0001) and AUC<sub>0-inf</sub> (p < 0.001) compared to the sildenafil group. After co-administration of sildenafil and ketoconazole, a significant increase in C<sub>max</sub>, AUC<sub>0-t</sub> and AUC<sub>0-inf</sub> was observed in both of the experiments.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":10961,\"journal\":{\"name\":\"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences\",\"volume\":\"30 1\",\"pages\":\"75-84\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114228/pdf/40199_2022_Article_433.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1007/s40199-022-00433-z\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s40199-022-00433-z","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Influence of methylxanthines isolated from Bancha green tea on the pharmacokinetics of sildenafil in rats.
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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