Effects of epigallocatechin gallate on the oral bioavailability and pharmacokinetics of tamoxifen and its main metabolite, 4-hydroxytamoxifen, in rats.
ABSTRACT The effects of epigallocatechin gallate (EGCG) on the oral bioavailability and pharmacokinetics of tamoxifen and its metabolite, 4-hydroxytamoxifen, were investigated in rats. A single dose of tamoxifen was administered intravenously (2 mg/kg) and orally (10 mg/kg) with or without epigallocatechin (0.5, 3 and 10 mg/kg) to rats. The presence of EGCG significantly altered the pharmacokinetics of orally administered tamoxifen. Compared with the oral control group (given tamoxifen alone), the area under the plasma concentration-time curve and the peak plasma concentration of tamoxifen significantly (P<0.05 for 3 mg/kg of EGCG, P<0.01 for 10 mg/kg of EGCG) increased 48.4-77.0 and 57.1-89.7%, respectively. Consequently, the absolute bioavailability of tamoxifen in the presence of EGCG (3 and 10 mg/kg) was 48.9-78.1%, which was significantly enhanced (P<0.05 for 3 mg/kg of EGCG, P<0.01 for 10 mg/kg of EGCG) compared with the oral control group (23.7%). Moreover, the relative bioavailability of tamoxifen was 1.48-1.77-fold greater than that of the control group. EGCG at a dose of 10 mg/kg significantly increased the area under the plasma concentration-time curve (P<0.05, 40.3%) of 4-hydroxytamoxifen, but the metabolite-parent ratio of 4-hydroxytamoxifen was also significantly altered (P<0.05 for 10 mg/kg of EGCG), implying that the formation of 4-hydroxytamoxifen was considerably affected by EGCG. The increase in bioavailability of tamoxifen is likely to be due to the decrease in first-pass metabolism in the intestine and liver by inhibition of P-glycoprotein and CYP3A by EGCG. The increase in oral bioavailability of tamoxifen in the presence of EGCG should be taken into consideration of potential drug interactions between tamoxifen and EGCG.
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ABSTRACT: Quetiapine is an atypical antipsychotic, used clinically in the treatment of schizophrenia, acute mania in bipolar disorders, and bipolar depression in adults. In this study, the effect of green tea extracts (GTE) on the pharmacokinetics of quetiapine (substrate of CYP3A4) was investigated in rats. Male Wistar albino rats received GTE (175 mg/kg) or saline (control) by oral gavage for 7 days before a single intragastric administration of 25 mg/kg quetiapine. Plasma concentrations of quetiapine were measured up to 12 h after its administration by a validated ultraperformance liquid chromatography-tandem mass spectroscopy. Pretreatment with GTE produced significant reductions in the maximum plasma concentration and area under the curve of quetiapine by 45% and 35%, respectively, compared to quetiapine alone. However, GTE did not produce significant change in elimination half-life and oral clearance of quetiapine. This study concluded that GTE may decrease the bioavailability of quetiapine when coadministered.Evidence-based Complementary and Alternative Medicine 01/2015; 2015:615285. DOI:10.1155/2015/615285 · 2.18 Impact Factor
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ABSTRACT: Hormone replacement therapy and selective estrogen receptor modulator are the most common therapy for women going through menopause. These therapies though popular fail to relieve withdrawal symptoms such as hot flashes, fatigue, leg cramps and nausea. This scenario necessitates to herbal preparations as alternative which may lead to simultaneous intake of herbal preparations, containing flavonoids, as well as Selective estrogen receptor modulator hence creating a phenomenon of herb drug interaction. Here we investigate the effect of red clover on steady state mRNA levels of rat cytochrome P 450 enzymes. Further, red clover's effect on cytochrome P 450's expression has been investigated when co-administered with tamoxifen and raloxifene. Exposure to red clover resulted in significant down regulation of all the cytochrome P 450 isoform mRNA except cytochrome P 450 2C13 and cytochrome P 450 3A2. When red clover is given in combination with tamoxifen or raloxifene altered level of cytochrome P 450 enzyme mRNA is observed. Present results suggest that herbal medical preparations such red clover has potential for herb drug interaction.Indian Journal of Pharmaceutical Sciences 05/2014; 76(3):261-6. · 0.30 Impact Factor
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ABSTRACT: Background and Objective In recent years, there has been a remarkable progress in understanding the pharmacological and toxicological impact of polyphenols and the possibility of pharmacokinetic polyphenols-drugs or trace elements interactions that may have undesirable therapeutic outcomes or may be desirable to reach specific targets. Accordingly, the present study was designed to evaluate both long-term and single dose effect of silibinin, epigallocatechin (ECGC), quercetin and rutin on the absorption and tissue distribution of drugs (metformin and atenolol) and trace elements (zinc, copper and iron) after single oral doses of each. Methods: In long term study, thirty rats were used, allocated into 5 groups and treated as follow: 1st group treated with olive oil and served as control; the other 4 groups were treated with either silibinin, EPGC, quercetin or rutin, administered orally as oily solutions for 30 days. At day 31, a solution contains sulphate salts of zinc, copper and iron was administered orally; meanwhile, a solution contains metformin and then atenolol were administered orally by gavage tube. In short term study, the same design was followed, where the same doses of the drugs and trace elements were administered after 30 days of treatment with the previously mentioned polyphenols, where single daily doses were orally administered; the effect was compared with that reported in vehicle treated control group. The animals were sacrificed and blood samples, tissues of brain, kidney and liver were obtained for evaluation of the plasma and tissues concentrations of metformin, atenolol, Zn, Cu and Fe using HPLC and atomic absorption spectrometry. Results: In long term study the results showed that all four polyphenols groups increased both serum and tissue levels of metformin but they had no effect on atenolol level compared with control group. Furthermore, serum and tissue concentrations of Zn, Cu and Fe were increased significantly compared with control. Meanwhile, in the single dose study, all four polyphenols groups decrease serum and tissues concentration of trace elements compared with control, and they also lead to increase serum and tissues levels of metformin without any significant effect on atenolol level. Conclusion: Both single doses and long-term use of supraphysiological doses of silibinin, EGCG, quercetin and rutin increased absorption and tissues availability of metformin but not atenolol, while opposite results were reported for trace elements, where long term use of polyphenols increased serum, brain, liver and kidney levels of Zn, Cu and Fe, while single dose study reveal a significant decrease in this respect.09/2012, Degree: PhD, Supervisor: Saad A. Hussain