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Prolonged\u2010release tacrolimus (PR\u2010Tac) is largely absorbed in distal intestinal segments and is less susceptible to CYP3A inhibition. The effect of induction by SJW is unknown. In this randomized, crossover trial, 18 healthy volunteers received single oral tacrolimus doses (immediate\u2010release [IR]\u2010Tac or PR\u2010Tac, 5\u00a0mg each) alone and during induction by SJW. Concentrations were quantified using ultra\u2010high performance liquid chromatography coupled with tandem mass spectrometry and non\u2010compartmental pharmacokinetics were evaluated. SJW decreased IR\u2010Tac exposure (area under the concentration\u2010time curve) to 73% (95% confidence interval 60%\u201088%) and maximum concentration (C<jats:sub>max<\/jats:sub>) to 61% (52%\u201073%), and PR\u2010Tac exposure to 67% (55%\u201081%) and C<jats:sub>max<\/jats:sub> to 69% (58%\u201082%), with no statistical difference between the 2 formulations. The extent of interaction appeared to be less pronounced in volunteers with higher baseline CYP3A4 activity and in CYP3A5 expressors. In contrast to CYP3A inhibition, CYP3A induction by SJW showed a similar extent of interaction with both tacrolimus formulations. A higher metabolic baseline capacity appeared to attenuate the extent of induction by SJW.<\/jats:p>","DOI":"10.1002\/cpdd.1364","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T02:23:43Z","timestamp":1704421423000},"page":"297-306","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effect of Tacrolimus Formulation (Prolonged\u2010Release vs Immediate\u2010Release) on Its Susceptibility to Drug\u2010Drug Interactions with St. John's Wort"],"prefix":"10.1002","volume":"13","author":[{"given":"Katja S.","family":"G\u00fcm\u00fcs","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacoepidemiology University of Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Teegelbekkers","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacoepidemiology 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