Effect of St John's wort on the pharmacokinetics of fexofenadine The effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum) Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: comparative effects of St. John's wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics. Hyperforin content determines the magnitude of the St John's Wort–cyclosporine drug interaction The treatment of minor depression with St. John's Wort or citalopram: failure to show benefit over placebo. Coordinate induction of both cytochrome P4503A and MDR1 by St John's wort in healthy subjects Different effects of St John's Wort on the pharmacokinetics of simvastatin and pravastatin The interaction between St John's wort and an oral contraceptive Differential therapy of mild to moderate depressive episodes (ICD-10 F 32.0; F 32.1) with St. John's wort. Cytochrome P450 phenotypic ratios for predicting herb‐drug interactions in humans
St John 's wort is a popular over‐the‐counter dietary supplement and herbal remedy that has been implicated in drug interactions with several substrates of P‐glycoprotein . The effect of St John 's wort on P‐glycoprotein activity in vivo was examined with use of fexofenadine as selective probe drug St John 's wort(Hypericum perforatum ) is a popular over‐the‐counter dietary supplement and herbal remedy that has been implicated in drug interactions with substrates of several cytochrome P450 ( CYP ) isozymes . The effect of St John 's wort on CYP activity in vivo was examined with a probe drug cocktail Extracts of St John 's wort ( Hypericum perforatum ) are widely used in the treatment of depression , often as an over‐the‐counter drug . In contrast to its frequent use , knowledge about the pharmacokinetics of ingredients and drug interactions of St John 's wort is poor . We studied the interaction between hypericum extract LI160 and digoxin Concomitant administration of botanical supplements with drugs that are P-glycoprotein ( P-gp ) substrates may produce clinical ly significant herb-drug interactions . This study evaluated the effects of St. John 's wort and Echinacea on the pharmacokinetics of digoxin , a recognized P-gp substrate . Eighteen healthy volunteers were r and omly assigned to receive a st and ardized St. John 's wort ( 300 mg three times daily ) or Echinacea ( 267 mg three times daily ) supplement for 14 days , followed by a 30-day washout period . Subjects were also r and omized to receive rifampin ( 300 mg twice daily , 7 days ) and clarithromycin ( 500 mg twice daily , 7 days ) as positive controls for P-gp induction and inhibition , respectively . Digoxin ( Lanoxin 0.25 mg ) was administered orally before and after 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 ) ) , elimination half-life , and maximum serum concentration were used to assess the effects of St. John 's wort , Echinacea , rifampin , and clarithromycin on digoxin disposition . St. John 's wort and rifampin both produced significant reductions ( p < 0.05 ) in AUC((0 - 3 ) ) , AUC((0 - 24 ) ) , and C(max ) , while clarithromycin increased these parameters significantly ( p < 0.05 ) . Echinacea supplementation did not affect digoxin pharmacokinetics . Clinical ly significant P-gp-mediated herb-drug interactions are more likely to occur with St. John 's wort than with Echinacea Hyperforin ( HYF ) has been discussed as a potential cause of the reduction in the bioavailability of numerous drugs seen with St John 's wort ( SJW ) comedication . This study compared the effects of 2 SJW preparations with high and low HYF content on the pharmacokinetics of cyclosporine ( INN , ciclosporin ) ( CSA ) This paper presents new data addressing two important controversies in psychiatry : the construct of Minor Depression ( MinD ) and the efficacy of St. John 's Wort for milder forms of depressive disorders . Data are from a three-arm , 12 week , r and omized clinical trial of investigating the efficacy of St. John 's Wort ( 810 mg/day ) , citalopram ( 20 mg/day ) , or placebo for acute treatment of MinD. Due to a high placebo response on all outcome measures , neither St. John 's Wort nor citalopram separated from placebo on change in depressive symptom severity , quality of life , or well-being . However , systematic assessment of potential adverse effects ( AEs ) led to three important observations : ( 1 ) prior to the administration of study compound , 60 % of subjects endorsed items that would be characterized as AEs once study compound was administered , ( 2 ) St. John 's Wort and citalopram were each associated with a significant number of new or worsening AEs during treatment , and ( 3 ) using a structured interview for identifying AEs at baseline and during treatment is informative . MinD was not responsive to either a conventional antidepressant or a nutraceutical , and both compounds were associated with a notable side effects burden . Other treatment approaches for MinD should be investigated Many drugs are cosubstrates of cytochrome P450 ( CYP ) 3A and MDR1 ; furthermore , their disposition is markedly affected by pretreatment with inducing agents , including St John 's wort . Such drug interactions reflect induction of both proteins through a common mechanism involving the steroid X receptor/pregnane X receptor . However , the relative contributions of enhanced metabolism and efflux transport to the overall induction process are unknown St John 's Wort , a widely used herbal product , is an inducer of CYP3A4 and it decreases blood concentrations of CYP3A4 substrates . The effects of St John 's Wort on the pharmacokinetics of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors simvastatin  ( an inactive lactone pro‐drug ) and pravastatin were determined in this study The popular herbal remedy St John 's wort is an inducer of cytochrome P450 ( CYP ) 3A enzymes and may reduce the efficacy of oral contraceptives . Therefore we evaluated the effect of St John 's wort on thedisposition and efficacy of Ortho‐Novum 1/35 ( Ortho‐McNeil Pharmaceutical , Inc , Raritan , NJ ) , a popular combination oral contraceptive pill containing ethinyl estradiol ( INN , ethinylestradiol ) and norethindrone ( INN , norethisterone ) The purpose of this report was to evaluate specific depressive symptoms that are most suitable for a therapy with the Ze 117 St. John 's wort extract . We examined the antidepressant efficacy and drug safety of Ze 117 and fluoxetine in a multicentric prospect i ve r and omized double-blind parallel group comparison according to generally accepted guidelines such as the Declaration of Helsinki and GCP . We treated out patients ( n = 240 ; Ze 117 : 126 ; fluoxetine : 114 ) with mild to moderate depressive episodes ( ICD-10 : F 32.0 , F 32.1 ; HAMD range : 16 - 24 ) with either two tablets St John 's wort ( Ze 117 ; 500 mg extract/day ) or fluoxetine ( 20 mg/day ) for 6 weeks . Antidepressant efficacy was evaluated with the vali date d HAMD psychometric method . A vali date d analysis of HAMD subscores was made to verify the efficacy for certain depressive symptoms . The main results were : * The HAMD responder rate was 60 % in the Ze 117 group compared to 40 % in the fluoxetine group ( p = 0.005 ) . * Particularly , there was a marked decrease of depressive agitation ( pre-post comparison : 46 % ) and anxiety symptoms ( 44 % ) during the therapy with St. John 's wort . Depressive obstruction ( 44 % ) and sleep disorders ( 43 % ) were reduced during the treatment , too . There were no statistically significant differences between the treatment groups . * Adverse events occurred in 28 patients ( 25 % ) in the fluoxetine group and in 18 ( 14 % ) of the St. John 's wort group ( p < 0.07 ) . St. John 's wort extract is a clinical ly effective equivalent to fluoxetine regarding overall depressive symptoms and main symptoms of depressive episodes . An especially interesting overall observation is that Ze 117 is particularly effective in depressive patients suffering from anxiety symptoms . St. John 's wort revealed better safety and tolerability data than fluoxetine 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 St John 's wort , garlic oil , Panax ginseng , and Ginkgo biloba affected CYP1A2 , CYP2D6 , CYP2E1 , or CYP3A4 activity
Clinicians and patients should beware of possible decreases in the systemic bioavailability of conventional drugs when taken concomitantly with St John 's wort
OBJECTIVE To determine the method ological quality of clinical trials that examined possible interactions of St John 's wort with conventional drugs , and to examine the results of these trials .