Hur påverkar johannesört farmakokinetiken utav warfarin, ciklosporin, digoxin, preventivmedel och teofyllin? Vad har detta för klinisk betydelse?
St. John?s wort extract is composed of a large number of components, about 150, but the most studied and interesting substance are hyperforin and hypericin. The herb is very popular and it is known for its pharmacological efficacy in numerous disorders. It is used for treatment of mild to moderated depression as an alternative to synthetic antidepressants. The St. John?s wort products are available in several preparations, as tablets, capsules, tea, fresh plant juice etc. Hyperforin is the part of St. John?s wort that gives the antidepressant effect through inhibition of reuptake of neurotransmitters such norepinephrine, serotonin, dopamine, GABA and L-glutamate.Since 1999, several case reports and clinical studies have demonstrated the interactions of St. John?s wort extract with other medical products, resulting in a decreased plasma concentration and potential therapeutics failure. The mechanism behind this is an interaction between St. John?s wort with intestinal and hepatic cytochrome P450 and P-glycoprotein, resulting in inducing these enzymes. In vitro investigations indicated that this induction is medicated by an interaction of hyperforin with the pregnane X receptor.Long-term co-medication of St. John?s wort extract reduces the bioavailability of wide variety of drugs, including digoxin, warfarin, cyclosporine, oral contraceptive and theophylline.The object of the present thesis was to investigate and describe the influence of St. John?s wort extract on the pharmacokinetics of the drugs mentioned above and what this pharmacokinetic interaction has for clinical consequences.Seven studies, with different numbers of participants, performed in different countries, were compiled to describe the effect of St. John?s wort on the drugs.The results from these studies showed that St. John?s wort extract affects the metabolism of these drugs by significant reducing theirs pharmacological effect. This decrease of the bioavailability and plasma concentration can be the results of intestinal and hepatic induction of CYP enzymes and p-glycoprotein. From these results I conclude that St. John?s wort should be used with caution and patients receiving these drugs should regularly monitory theirs plasma concentration.