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Steroids induce CYP3A genes to increase tacrolimus clearance, but the effect is variable. We hypothesized that the extent of the steroid\u2013tacrolimus DDI differs by CYP3A4\/5 genotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Kidney transplant recipients (<jats:italic>n<\/jats:italic>\u2009=\u20092462) were classified by the number of loss of function alleles (LOF) (<jats:italic>CYP3A5*3<\/jats:italic>, <jats:italic>*6<\/jats:italic> and <jats:italic>*7<\/jats:italic> and <jats:italic>CYP3A4*22<\/jats:italic>) and steroid use at each tacrolimus trough in the first 6\u00a0months post\u2010transplant. A population pharmacokinetic analysis was performed by nonlinear mixed\u2010effect modelling (NONMEM) and stepwise covariate modelling to define significant covariates affecting tacrolimus clearance. A stochastic simulation was performed and translated into a Shiny application with the mrgsolve and Shiny packages in R.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Steroids were associated with modestly higher (3%\u201311.8%) tacrolimus clearance. Patients with 0\u2010LOF alleles receiving steroids showed the greatest increase (11.8%) in clearance compared to no steroids, whereas those with 2\u2010LOFs had a negligible increase (2.6%) in the presence of steroids. Steroid use increased tacrolimus clearance by 5% and 10.3% in patients with 1\u2010LOF and 3\/4\u2010LOFs, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Steroids increase the clearance of tacrolimus but vary slightly by CYP3A genotype. This is important in individuals of African ancestry who are more likely to carry no LOF alleles, may more commonly receive steroid treatment, and will need higher tacrolimus doses.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16172","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T10:59:12Z","timestamp":1720781952000},"page":"2837-2848","source":"Crossref","is-referenced-by-count":9,"title":["Steroid\u2013tacrolimus drug\u2013drug interaction and the effect of CYP3A genotypes"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8280-1375","authenticated-orcid":false,"given":"Abdelrahman","family":"Saqr","sequence":"first","affiliation":[{"name":"Experimental and Clinical Pharmacology University of Minnesota College of Pharmacy  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5458-0712","authenticated-orcid":false,"given":"Mahmoud","family":"Al\u2010Kofahi","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology University of Minnesota College of Pharmacy  Minneapolis Minnesota USA"},{"name":"Gilead Sciences, Inc.  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