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Both drugs are known to have remarkable renal uptake transporter\u2010mediated clearance. Owing to the lack of clinical studies on drug\u2013drug interaction between the 2 drugs, we conducted a translational clinical study to investigate the effect of PAS on tenofovir pharmacokinetics (PK).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Initially, we studied in vitro renal uptake transporter\u2010mediated drug\u2013drug interactions using stably transfected cells with human organic anion transporters (OAT1 and OAT3). Later, we estimated clinical drug interactions using static and physiologically based PK modelling. Finally, we investigated the effects of PAS\u2010calcium formulation (PAS\u2010Ca) on tenofovir disoproxil fumarate PK in healthy male Korean subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PAS inhibited OAT1\u2010 and OAT3\u2010mediated tenofovir uptake in vitro. The physiologically based PK drug\u2013drug interaction model suggested a 1.26\u2010fold increase in tenofovir peak plasma concentration when coadministered with PAS. By contrast, an open\u2010label, randomized, crossover clinical trial evaluating the effects of PAS\u2010Ca on tenofovir PK showed significantly altered geometric mean ratio (90% confidence intervals) of maximum plasma concentration (C<jats:sub>max<\/jats:sub>) and area under the curve (AUC<jats:sub>0\u2010inf<\/jats:sub>) by 0.33 (0.28\u20130.38) and 0.29 (0.26\u20130.33), respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study findings suggest that the PAS\u2010Ca formulation significantly reduced systemic exposure to tenofovir through an unexplained mechanism, which was contrary to the initial prediction. Caution should be exercised while predicting in vivo PK profiles from in vitro data, particularly when there are potential confounders such as pharmaceutical interactions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15056","type":"journal-article","created":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T13:24:16Z","timestamp":1629897856000},"page":"1159-1169","source":"Crossref","is-referenced-by-count":4,"title":["Para\u2010aminosalicylic acid significantly reduced tenofovir exposure in human subjects: Mismatched findings from in vitro to in vivo translational research"],"prefix":"10.1111","volume":"88","author":[{"given":"Md Masud","family":"Parvez","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology, PharmacoGenomics Research Center Inje University College of Medicine  Busan Republic of Korea"},{"name":"Center for Personalized Precision Medicine of Tuberculosis Inje University College of Medicine  Busan Republic of 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