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.
- SourceAvailable from: Wojciech Leppert[Show abstract] [Hide abstract]
ABSTRACT: Oxycodone is a valued opioid analgesic, which may be administered either as the first strong opioid or when other strong opioids are ineffective. In case of insufficient analgesia and/or intense adverse effects such as sedation, hallucinations and nausea/vomiting a switch from another opioid to oxycodone might be beneficial. Oxycodone is administered to opioid-naive patients with severe pain and to patients who were unsuccessfully treated with weak opioids, namely tramadol, codeine and dihydrocodeine. Oxycodone effective analgesia may be attributed to its affinity to μ and possibly κ opioid receptors, rapid penetration through the blood-brain barrier and higher concentrations in brain than in plasma. Oxycodone displays high bioavailability after oral administration and may be better than morphine in patients with renal impairment due to the decreased production of active metabolites. Recently an oral controlled-release oxycodone formulation was introduced in Poland. Another new product that was launched recently is a combination of prolonged-release oxycodone with prolonged-release naloxone (oxycodone/naloxone tablets). The aim of this review is to outline the pharmacodynamic and pharmacokinetic properties, drug interactions, dosing rules, adverse effects, equianalgesic dose ratio with other opioids and clinical studies of oxycodone in patients with cancer pain. The potential role of oxycodone/naloxone in chronic pain management and its impact on the bowel function is also discussed.Pharmacological reports: PR 07/2010; 62(4):578-91. DOI:10.1016/S1734-1140(10)70316-9 · 2.17 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The aim of this study was to investigate the effect of the cytochrome P450 3A4 inhibitor clarithromycin on the pharmacokinetics and pharmacodynamics of oral oxycodone in young and elderly subjects. Ten young and 10 elderly healthy subjects participated in this placebo-controlled, randomized, 2-phase crossover study. Subjects took clarithromycin 500 mg or placebo twice daily for 5 days. On day 4, subjects ingested an oral dose of 10 mg oxycodone. Plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 hours, and pharmacological response for 12 hours. Clarithromycin decreased the apparent clearance of oxycodone by 53% in young and 48% in elderly subjects (P < 0.001) and prolonged its elimination half-life. The mean area under the plasma concentration-time curve (AUC0-∞) of oxycodone was increased by 2.0-fold (range, 1.3-fold to 2.7-fold) (P < 0.001) in young and 2.3-fold (range, 1.1-fold to 3.8-fold) (P < 0.001) in elderly subjects. The formation of noroxycodone was decreased by 74% in young and 71% in elderly subjects (P < 0.001). The ratio of AUC0-∞ of oxycodone during the clarithromycin phase compared with the one with placebo did not differ between the age groups. Clarithromycin did not alter the pharmacological response to oxycodone. Clarithromycin increased the exposure to oral oxycodone, but the magnitude of this effect was not age related. Although the pharmacological response to oxycodone was not significantly influenced by clarithromycin, dose reductions may be necessary in the most sensitive patients to avoid adverse effects when oxycodone is used concomitantly with clarithromycin.Journal of clinical psychopharmacology 06/2011; 31(3):302-8. DOI:10.1097/JCP.0b013e3182189892 · 3.76 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Ketamine is an intravenous anaesthetic and analgesic agent but it can also be used orally as an adjuvant in the treatment of chronic pain. This study investigated the effect of the herbal antidepressant St John's wort, an inducer of cytochrome P450 3A4 (CYP3A4), on the pharmacokinetics and pharmacodynamics of oral S-ketamine. In a randomized cross-over study with two phases, 12 healthy subjects were pretreated with oral St John's wort or placebo for 14 days. On day 14, they were given an oral dose of 0.3 mg/kg of S-ketamine. Plasma concentrations of ketamine and norketamine were measured for 24 h and pharmacodynamic variables for 12 h. St John's wort decreased the mean area under the plasma concentration-time curve (AUC(0-∞) ) of ketamine by 58% (P < 0.001) and decreased the peak plasma concentration (C(max) ) of ketamine by 66% (P < 0.001) when compared with placebo. Mean C(max) of norketamine (the major metabolite of ketamine) was decreased by 23% (P = 0.002) and mean AUC(0-∞) of norketamine by 18% (P < 0.001) by St John's wort. There was a statistically significant linear correlation between the self-reported drug effect and C(max) of ketamine (r = 0.55; P < 0.01). St John's wort greatly decreased the exposure to oral S-ketamine in healthy volunteers. Although this decrease was not associated with significant changes in the analgesic or behavioural effects of ketamine in the present study, usual doses of S-ketamine may become ineffective if used concomitantly with St John's wort.Fundamental and Clinical Pharmacology 06/2011; 26(6). DOI:10.1111/j.1472-8206.2011.00954.x · 2.08 Impact Factor