***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Phytochemical‐mediated modulation of cytochrome P450 ( CYP ) activity may underlie many herb‐drug interactions . Single‐time point phenotypic metabolic ratios were used to determine whether long‐term supplementation of Citrus aurantium , Echinacea purpurea , milk thistle ( Silybum marianum ) , or saw palmetto ( Serenoa repens ) extracts affected CYP1A2 , CYP2D6 , CYP2E1 , or CYP3A4 activity Phytochemical-mediated modulation of P-glycoprotein ( P-gp ) and other drug transporters may give rise to many herb-drug interactions . Serial plasma concentration-time profiles of the P-gp substrate , digoxin , were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo . Twenty healthy volunteers were r and omly assigned to receive a st and ardized goldenseal ( 3210 mg daily ) or kava kava ( 1227 mg daily ) supplement for 14 days , followed by a 30-day washout period . Subjects were also r and omized to receive rifampin ( 600 mg daily , 7 days ) and clarithromycin ( 1000 mg daily , 7 days ) as positive controls for P-gp induction and inhibition , respectively . Digoxin ( Lanoxin , 0.5 mg ) was administered p.o . before and at the end of each supplementation and control period . Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay . Comparisons of area under the curve (AUC)(0–3 ) , AUC(0–24 ) , Cmax , CL/F , and elimination half-life were used to assess the effects of goldenseal , kava kava , rifampin , and clarithromycin on  digoxin pharmacokinetics .  Rifampin produced significant reductions ( p < 0.01 ) in AUC(0–3 ) , AUC(0–24 ) , CL/F , t1/2 , and Cmax , whereas clarithromycin increased these parameters significantly ( p < 0.01 ) . With the exception of goldenseal 's effect on Cmax ( 14 % increase ) , no statistically significant effects on  digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava . When compared with rifampin and clarithromycin , supplementation with these specific formulations of goldenseal or kava kava did not appear to affect  digoxin pharmacokinetics , suggesting that these supplements are not potent modulators of P-gp in vivo Milk thistle ( Silybum marianum ) extracts are widely used as a complementary and alternative treatment of various hepatic conditions and a host of other diseases/disorders . The active constituents of milk thistle supplements are believed to be the flavonolignans contained within the extracts . In vitro studies have suggested that some milk thistle components may significantly inhibit specific cytochrome P450 ( P450 ) enzymes . However , determining the potential for clinical ly significant drug interactions with milk thistle products has been complicated by inconsistencies between in vitro and in vivo study results . The aim of the present study was to determine the effect of a st and ardized milk thistle supplement on major P450 drug-metabolizing enzymes after a 14-day exposure period . CYP1A2 , CYP2C9 , CYP2D6 , and CYP3A4/5 activities were measured by simultaneously administering the four probe drugs , caffeine , tolbutamide , dextromethorphan , and midazolam , to nine healthy volunteers before and after exposure to a st and ardized milk thistle extract given thrice daily for 14 days . The three most abundant falvonolignans found in plasma , following exposure to milk thistle extracts , were silybin A , silybin B , and isosilybin B. The concentrations of these three major constituents were individually measured in study subjects as potential perpetrators . The peak concentrations and areas under the time-concentration curves of the four probe drugs were determined with the milk thistle administration . Exposure to milk thistle extract produced no significant influence on CYP1A2 , CYP2C9 , CYP2D6 , or CYP3A4/5 activities Objective Induction of CYP3A by St. John ’s wort ( SJW ) extracts with high hyperforin ( HYF ) content is well described . Since SJW products vary in the amount of HYF and other main constituents , the aim of the study was to evaluate the effect on CYP3A function of SJW preparations with a range from very low to high HYF content . Methods Forty-two male , healthy volunteers were r and omized into six parallel SJW medication groups with varying composition especially with regard to HYF content .  Midazolam plasma concentration profiles were characterized after a single oral dose of 7.5 mg midazolam on the day before and on the 14th day of SJW medication . Results All SJW preparations tested result ed in a decrease in midazolam AUC , although the extent of the effect differed . The extract LI 160 ( HYF 41 mg/day ) decreased midazolam AUC0–12h by 79.4 % ( 95 % CI −88.6 ; −70.1 ) , which was significantly greater than the effect by any other medication ( p<0.05 ) . SJW powder tablets 2.7 g/day ( HYF 12 mg/day ) result ed in a midazolam AUC0–12h decrease of 47.9 % ( 95 % CI −59.7;−36.2 ) , while 2.7 g/day SJW powder tablets that were almost devoid of HYF ( 0.13 mg/day ) reduced midazolam AUC0–12h by only 21.1 % ( 95 % CI −33.9 ; −8.3 ) . Considering all six SJW medications tested , the extent of midazolam AUC decrease correlated significantly with increasing HYF dose ( r=−0.765 , p<0.001 ) , but not with hypericin dose ( r=−0.067 ; p=0.673 ) . Conclusion The extent of induction of CYP3A varies among St. John ’s wort products and depends on hyperforin dose ETHNOPHARMACOLOGY Herb-drug interactions may potentially affect drug efficacy and /or the likelihood of adverse drug reactions .  Radix Astragali ( RA ) extract formulation is usually prescribed for long-term use for patients with immunodeficiency , diabetes , nephropathy or cardiovascular diseases . Its use in combination with P-glycoprotein ( P-gp ) substrates is possible in clinical practice . Currently there is little knowledge about whether concomitant use of RA extract has an influence on disposition of P-gp substrate . AIM OF THE STUDY This study was to investigate whether continuous and multiple doses of RA extract granules had modulatory effects on human P-gp . MATERIAL AND METHODS A r and omised , placebo-controlled , two-period crossover pharmacokinetic drug interaction study was conducted in healthy Chinese volunteers .  Fexofenadine was used as a P-gp phenotyping probe . Fourteen volunteers received RA extract granules or placebo ( 4 g bid ) for 7 days and then received a single oral dose of 120 mg fexofenadine . Fexofenadine plasma concentrations were determined by HPLC . Pharmacokinetic parameters were calculated by non-compartmental method and bioequivalence evaluation was performed . RESULTS Pharamcokinetic parameters in the placebo phase were as follows : T1/2 ( 3.75±1.47h ) , Cmax ( 745.11±137.41μg/L ) , Tmax ( 2.25±0.47h ) , AUC(0-t ) ( 3894.27±923.45μgh/L ) , AUC(0-∞ ) ( 3993.84±912.97μgh/L ) . Pharamcokinetic parameters in the RA extract phase were as follows : T1/2 ( 4.00±1.24h ) , Cmax ( 709.44±170.03μg/L ) , Tmax ( 2.21±0.51h ) , AUC(0-t ) ( 3832.72±1077.60μgh/L ) , AUC(0-∞ ) ( 3983.53±1019.83μgh/L ) . The influence of RA extract on fexofenadine Cmax and AUC lacks statistical significance . Fexofenadine in the two phases were bioequivalent . In the placebo phase , T1/2 of fexofenadine in ABCB1 3435 T mutation allele carriers was longer compared to ABCB1 3435CC carriers ( 4.43±1.44h vs. 2.54±0.21h , p<0.05 ) . However , RA extract pretreatment abolished such genotype-related difference due to the lengthened T1/2 in ABCB1 3435CC carriers . There was no association of the C3435 T polymorphism with Cmax and AUC(0-t ) in subjects with two pretreatments . CONCLUSION One-week administration of RA extract granules did not have a statistically significant impact on systematic exposure to fexofenadine , suggesting that RA extract is not a potent modulator of P-gp in vivo . RA extract appears to have ABCB1 C3435 T genotype-dependent inhibitory effect on elimination rather than absorption of a P-gp substrate . Further investigations are necessary in patients who receive long-term use of RA extract formulation and combined P-gp substrates , especially in those ABCB1 3435CC carriers Controlled trials that use r and omized allocation are the best tool to control for bias and confounding in trials testing clinical interventions . Investigators must be sure to include information that is required by the reader to judge the validity and implication s of the findings in the reports of these trials . In part , complete reporting of trials will allow clinicians to modify their clinical practice to reflect current evidence toward the improvement of clinical outcomes . The consoli date d st and ards of reporting trials ( CONSORT ) statement was developed to assist investigators , authors , review ers , and editors on the necessary information to be included in reports of controlled clinical trials . The CONSORT statement is applicable to any intervention , including herbal medicinal products . Controlled trials of herbal interventions do not adequately report the information suggested in CONSORT . Recently , reporting recommendations were developed in which several CONSORT items were elaborated to become relevant and complete for r and omized controlled trials of herbal medicines . We expect that these recommendations will lead to more complete and accurate reporting of herbal trials . We wrote this explanatory document to outline the rationale for each recommendation and to assist authors in using them by providing the CONSORT items and the associated elaboration , together with examples of good reporting and empirical evidence , where available , for each . These recommendations for the reporting of herbal medicinal products presented here are open to revision as more evidence accumulates and critical comments are collected Purpose The aim of the present study is to investigate a possible role of a single dose of (−)-epigallocatechin gallate ( EGCG ) , the major catechin in green tea , for the pharmacokinetic interaction between green tea and nadolol in humans . Methods In a r and omized three-phase crossover study , 13 healthy volunteers received single doses of 30 mg nadolol orally with water ( control ) , or an aqueous solution of EGCG-concentrated green tea extract ( GTE ) at low or high dose . Plasma concentrations and urinary excretion of nadolol were determined up to 48 h. In addition , blood pressure and pulse rate were monitored . In vitro transport kinetic experiments were performed using human embryonic kidney 293 cells stably expressing organic anion transporting polypeptide (OATP)1A2 to evaluate the inhibitory effect of EGCG on OATP1A2-mediated substrate transport . Results Single coadministration of low and high dose GTE significantly reduced the plasma concentrations of nadolol . The geometric mean ratios with 90 % CI for area under the plasma concentration – time curves from 0 to infinity of nadolol were 0.72 ( 0.56–0.87 ) for the low and 0.60 ( 0.51–0.69 ) for the high dose . There were no significant differences in Tmax , elimination half-life , and renal clearance between GTE and water phases . No significant changes were observed for blood pressure and pulse rate between phases . EGCG  competitively inhibited OATP1A2-mediated uptake of sulphobromophthalein and nadolol with Ki values of 21.6 and 19.4 μM , respectively . Conclusions EGCG is suggested to be a key contributor to the interaction of green tea with nadolol . Moreover , even a single coadministration of green tea may significantly affect nadolol pharmacokinetics Background The activity of ginger in the management of chemotherapy-induced nausea and vomiting ( CINV ) has been suggested , but design inadequacies , heterogeneity of the population , small numbers and poor quality of tested products limit the possibility to offer generalizable results . Patients and methods We conducted a r and omized , double-blind , placebo-controlled , multicenter study in patients planned to receive ≥2 chem 
    Output:
    
Green tea ( GT ) showed significant 85 % decrease in plasma concentration of nadolol .
The study findings suggest that GT , SJW and EP perpetuate significant interactions with prescribed medications via CYP3A4 or OATP1A2 .