## 5 De Novo Synthesis of EGCG and Methods of Isolation
\begin{table}
\begin{tabular}{c c c} \hline \hline \multicolumn{3}{c}{**Therapeutic Group**} \\ \hline
**Drug Name** & **Route of** & **Animal Studies** & **Clinical Studies** \\ _Administration_ & & \\ \hline \multicolumn{3}{c}{**psycholeptics**} \\ \hline alprazolam & & [GTE] no significant change in alprazolam \\ _po_ & & pharmacokinetics [100] \\ buspirone & & [GTE] \(\uparrow\)AUC [101] \\ _po_ & & \\ clozapine & & \\ _po_ & [GTE] \(\downarrow\)AUC, \(\downarrow\)C\({}_{\text{max}}\)[102] & \\ midazolam & & \\ _iv_ & [GTE] \(\downarrow\)t\({}_{1/2}\), \(\uparrow\)ke [103] & \\ midazolam & & \\ _po_ & [GTE] \(\uparrow\)AUC, \(\uparrow\)C\({}_{\text{max}}\), \(\downarrow\)CL [103] & \\ quetiapine & & \\ _po_ & [GTE] \(\downarrow\)AUC, \(\downarrow\)C\({}_{\text{max}}\)[104] & \\ \hline \multicolumn{3}{c}{**other**} \\ \hline caffeine & & [GTE] no significant change in caffeine plasma \\ _po_ & & concentration [101] \\  & [EGCG] \(\uparrow\)C\({}_{\text{max}}\), \(\uparrow\)AUC (smaller dose 3–30 & \\ cyclosporine A & mg\(\cdot\)kg\({}^{-1}\)) & \\ _iv \& po_ & [EGCG] \(\downarrow\)C\({}_{\text{max}}\), \(\downarrow\)AUC, \(\uparrow\)CL (higher dose 100 & \\  & mg\(\cdot\)kg\({}^{-1}\)) [105] & \\ dextromethorphan & & \\ _po_ & & [GTE] no significant change in dextrometorfan \\  & & metabolic ratio [100] \\ digoxin & & [GTE] \(\downarrow\)AUC, \(\downarrow\)C\({}_{\text{max}}\)[81] \\ _po_ & & [GTE] \(\downarrow\)AUC, \(\downarrow\)C\({}_{\text{max}}\), no significant change in \\ lisinopril & & \(\text{t}_{\text{max}}\) or CL, the amount of lisinopril excreted into \\ _po_ & & urine over 24 h in the GTE phase was \\  & & significantly reduced [106] \\  & & [GTE] no significant change in urine losartan \\  & & levels [101] \\ metformin & & [EGCG] \(\uparrow\)serum level, higher tissues \\  & _po_ & distribution [96] \\ oxcarbazepine & & [EGCG] \(\downarrow\)AUC, \(\downarrow\)C\({}_{\text{max}}\)[107] \\ _ip_ & & \\ ticagrelor & & [GTE] no significant differences in the \\  & _iv_ & pharmacokinetic parameters [108] \\ ticagrelor & & [GTE] \(\downarrow\)AUC, \(\downarrow\)C\({}_{\text{max}}\), \(\uparrow\)CL, no difference in \\ _po_ & & \(\text{t}_{1/2}\)[108] \\ sildenafil & & \\ _po_ & & [GTE] \(\uparrow\)AUC, \(\uparrow\)C\({}_{\text{max}}\), \(\uparrow\)t\({}_{1/2}\), \(\downarrow\)k\({}_{\text{e}}\)[79] \\ tacrolimus & & [EGCG] \(\downarrow\)C\({}_{\text{max}}\), \(\downarrow\)AUC, \(\uparrow\)CL [105] \\ _iv_ & & \\ tacrolimus & & [EGCG] \(\downarrow\)C\({}_{\text{max}}\), (regardless of the dose) \\ _po_ & \(\downarrow\)AUC, \(\uparrow\)CL (higher dose 100 mg\(\cdot\)kg\({}^{-1}\)) [105] & \\ Tamoxifen & & [GTE] no significant differences in the \\ _po_ & & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: _Cont._Some studies also indicate that the intensity of observed changes may be related to the dose administered [77; 98]. The exact time between taking the drug and drinking green tea that could be considered safe is also unknown. In some studies, the wash-out period was established at 3-days [74], while in others at 7-days [100; 103; 110]. Changes in pharmacokinetic parameters of intravenously administered midazolam were observed even after a week [103]. However, the above-listed potential interactions may occur between EGCG and drugs, which should be taken on a daily basis. [PERSON] et al. [74] suggested that both regular and occasional intake of GTE may affect other drug pharmacokinetics. In addition, [PERSON] et al. [99] stated that observed changes might persist even 1 h after drinking a cup of green tea. These findings cannot be extrapolated to all patients for the following reasons. First, clinical trials conducted so far are usually carried out in small groups of healthy volunteers. Secondly, the high inter-individual variability of CYP450 and diverse consumption of green tea depends on the country [80] and seems to form an additional uncontrolled factor. What is interesting, and was indicated by [PERSON] et al. [98], is that interethnic differences cannot be excluded either.