St John's wort greatly reduces the concentrations of oral oxycodone.
ABSTRACT Chronic pain is associated with depression. Self-treatment of depression with herbal over-the-counter medicine St John's wort makes pain patients prone to drug interactions.
The aim of this study was to assess the potential of St John's wort to alter the CYP3A-mediated metabolism of a mu-opioid receptor agonist, oxycodone.
The study design was placebo-controlled, randomized, cross-over with two phases at intervals of 4 weeks and was conducted with 12 healthy participants. St John's wort (Jarsin) or placebo was administered t.i.d. for 15 days and oral oxycodone hydrochloride 15 mg on day 14. Oxycodone pharmacokinetics and pharmacodynamics were compared after St John's wort or placebo. Behavioural and analgesic effects were assessed with subjective visual analogue scales and cold pressor test. Plasma drug concentrations were measured from 0 to 48 h, behavioural and analgesic effects from 0 to 12 h.
Following St John's wort administration the oxycodone AUC decreased 50% (p<0.001). Oxycodone elimination half-life shortened from a mean+/-SD 3.8+/-0.7 to 3.0+/-0.4h (p<0.001). The self-reported drug effect of oxycodone as measured by AUEC(0-12) decreased significantly (p=0.004). Differences between St John's wort and placebo phases in cold pain threshold and intensity AUEC(0-12) were not observed.
St John's wort greatly reduced the plasma concentrations of oral oxycodone. The self-reported drug effect of oxycodone decreased significantly. This interaction may potentially be of some clinical significance when treating patients with chronic pain.
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ABSTRACT: Hypericum perforatum (HP) belongs to the Hypericaceae family and is one of the oldest used and most extensively investigated medicinal herbs. The medicinal form comprises the leaves and flowering tops of which the primary ingredients of interest are naphthodianthrones, xanthones, flavonoids, phloroglucinols (e.g. hyperforin), and hypericin. Although several constituents elicit pharmacological effects that are consistent with HP's antidepressant activity, no single mechanism of action underlying these effects has thus far been found. Various clinical trials have shown that HP has a comparable antidepressant efficacy as some currently used antidepressant drugs in the treatment of mild/moderate depression. Interestingly, low-hyperforin-content preparations are effective in the treatment of depression. Moreover, HP is also used to treat certain forms of anxiety. However, HP can induce various cytochrome P450s isozymes and/or P-glycoprotein, of which many drugs are substrates and which are the main origin of HP-drug interactions. Here, we analyse the existing evidence describing the clinical consequence of HP-drug interactions. Although some of the reported interactions are based on findings from in vitro studies, the clinical importance of which remain to be demonstrated, others are based on case reports where causality can, in some cases, be determined to reveal clinically significant interactions that suggest caution, consideration, and disclosure of potential interactions prior to informed use of HP. Copyright © 2013 John Wiley & Sons, Ltd.Phytotherapy Research 05/2014; 28(5). DOI:10.1002/ptr.5050 · 2.40 Impact Factor
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ABSTRACT: Use of dietary supplements (DS) during hospitalization carries risks such as reducing drug treatment efficacy and increasing peri-operative complications due to DS-drug interactions and DS side effects. In this study, we aimed to develop socio-cultural-sensitive patient histories to detect DS use amongst hospitalized patients from different backgrounds. Prospective cohort study of hospitalized patients from June 2009 through March 2010, using mixed quantitative (questionnaires), and qualitative (semi-structured interviews) research methodology to detect DS use. Data were provided by 691 of 895 patients (response rate 77.2%). Of these, 359 (51.9%) reported using DS in the previous year. 168 (46.8%) disclosed DS use following a standard question on DS consumption. 191 (53.2%) respondents disclosed DS use only following further questioning utilizing DS-related keywords. Leading questioning techniques that facilitated admitting DS use included: naming common DS (50.6% disclosure rate), and using traditional/herbal medicine (THM) related keywords (41.3% disclosure rate) such as infusions, teas, herbs picked in the garden. A logistic multivariate regression model indicated that disclosure of DS use, by using THM related keywords was associated with non-Jewish religion [EXP(B)=3.57, 95% C.I. 1.70-7.50, p=0.001], dwelling in rural areas (p=0.004), and having a lower degree of education (p=0.01). Improved history taking regarding DS use in hospitalized patients can be accomplished by using specific keywords that address socio-cultural diversities as in the following question: "Do you use any natural, folk, traditional, grandma remedies, herbs picked in the garden, infusions or herbal teas to improve your health?.Complementary therapies in medicine 04/2014; 22(2):304-10. DOI:10.1016/j.ctim.2014.01.005 · 2.22 Impact Factor
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ABSTRACT: In vitro inhibition of oxycodone metabolism to noroxycodone and oxymorphone and R- and S-methadone metabolism to R- and S-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) was measured for four H2-receptor antagonists and five proton-pump inhibitors (PPIs) using human liver microsomes (HLM) and cDNA-expressed human cytochrome P450s (rCYPs). Inhibitors were first incubated with HLM at three concentrations with and without preincubation of inhibitor, enzyme source and reducing equivalents to also screen for time-dependent inhibition (TDI). Cimetidine and famotidine (10-1,000 µM) inhibited all the four pathways >50%. Nizatidine and ranitidine did not. All the five PPIs (1-200 µM) inhibited one or more pathways >50%. Half maximal inhibitory concentrations (IC50s) were then determined using rCYPs. Cimetidine and famotidine both inhibited CYP3A4-mediated formation of noroxycodone and CYP2D6-mediated formation of oxymorphone, and famotidine inhibited CYP3A4-mediated formation of R- and S-EDDP, but IC50s were so high that only >10× therapeutic concentrations may have potential for reversible in vivo inhibition. The PPIs were more potent inhibitors; many have the potential for reversible in vivo inhibition at therapeutic concentrations. Omeprazole, esomeprazole and pantoprazole had greater effects on CYP3A4-mediated reactions, whereas lansoprazole was selective for CYP2D6-mediated formation of oxymorphone. Preincubation enhanced cimetidine inhibition of noroxycodone formation and rabeprazole inhibition of all pathways. Future studies will explore irreversible TDI.Journal of analytical toxicology 07/2013; 37(8). DOI:10.1093/jat/bkt060 · 2.63 Impact Factor