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

• Published in: Daru Vol. 30; no. 1; pp. 75 - 84
• Main Authors: Radeva-llieva, Maya, Stoeva, Stanila, Hvarchanova, Nadezhda, Zhelev, Iliya, Georgiev, Kaloyan D.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-06-2022; BioMed Central Ltd; Springer Nature B.V
• Subjects: Administration, Oral; Animals; Biomedical and Life Sciences; Biomedicine; Caffeine; Cytochrome P-450; Cytochrome P-450 CYP3A - metabolism; Drug interactions; Green tea; Herbs; High performance liquid chromatography; Ketoconazole; Liver; Male; Medicinal Chemistry; Medicine, Botanic; Medicine, Herbal; Pharmaceutical Sciences/Technology; Pharmacokinetics; Pharmacology/Toxicology; Pulmonary hypertension; Rats; Research Article; Sexual disorders; Sildenafil Citrate; Tea; Tea - chemistry; Xanthines; green tea; Drug-herb interactions; Methylxanthines; Sildenafil; Pharmacokinetics; Bancha green tea
• ISSN: 2008-2231; 1560-8115; 2008-2231
• DOI: 10.1007/s40199-022-00433-z

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
C
max
(
p
 > 0.05), AUC
0-t
(
p
 < 0.05) and AUC
0-inf
(
p
 < 0.05), while the administration of sildenafil after methylxanthines pretreatment resulted in an increase in
C
max
(
p
 < 0.0001), AUC
0-t
(
p
 < 0.0001) and AUC
0-inf
(
p
 < 0.001) compared to the sildenafil group. After co-administration of sildenafil and ketoconazole, a significant increase in
C
max
, AUC
0-t
and AUC
0-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.
Graphical abstract