Article

St John's wort greatly reduces the concentrations of oral oxycodone

Department of Anesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University Hospital and University of Turku, Turku, Finland.
European journal of pain (London, England) (Impact Factor: 2.93). 09/2010; 14(8):854-9. DOI: 10.1016/j.ejpain.2009.12.007
Source: PubMed

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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    • "The severity of oxycodone use/misuse was well documented by the Drug Abuse Warning Network, which reported a total of 1014 oxycodonerelated deaths in a 3-year period (Cone et al., 2003). Ninety percent of these oxycodone-related deaths were attributed to DDIs that can be transporters/DME mediated (Burrows et al., 2003; Cone et al., 2003, 2004; Lee et al., 2006; Nakazawa et al., 2010; Nieminen et al., 2010). We used microarrays to obtain a global profile of genes (including XRs, transporters, and DMEs) regulated in liver tissue of oxycodone treated rats. "
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