{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T12:46:43Z","timestamp":1761396403651},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Kidney allograft survival remains poorer in Black compared to White recipients due to racial differences in calcineurin inhibitor (CNI) pharmacology. P\u2010glycoprotein (P\u2010gp), an ABC efflux transporter expressed in peripheral blood mononuclear cells (PBMCs), modulates CNI pharmacokinetics and intracellular pharmacology. This study investigated P\u2010gp function in PBMC ex vivo at 0 (trough), 4, 8, and 12\u2009h in stable Black and White male and female kidney transplant recipients (<jats:italic>n<\/jats:italic>\u00a0=\u00a067) receiving tacrolimus and mycophenolic acid. Tacrolimus doses were adjusted to troughs of 4\u201310\u00a0ng\/ml. P\u2010gp function was quantified with flow cytometric measurement of cyclosporine (CYA; 2.5\u00a0\u03bcM)\u2010reversible efflux of P\u2010gp substrate, 3,3\u2032\u2010Diethyloxacarbocyanine iodide by determining the percentage change of mean fluorescent intensity (MFI) with CYA (% \u0394MFI). The composite parameter of area under the concentration versus time (AUC)<jats:sub>0\u201312h<\/jats:sub> % \u0394MFI estimated P\u2010gp function. Data analysis examined race, sex, and race\u2010sex associations to P\u2010gp function. A secondary aim analyzed <jats:italic>ABCB1<\/jats:italic> genotypes: <jats:italic>1236C&gt;T<\/jats:italic> (<jats:italic>rs1128503<\/jats:italic>), <jats:italic>2677G&gt;T\/A<\/jats:italic> (<jats:italic>rs2032582<\/jats:italic>), <jats:italic>3435C&gt;T<\/jats:italic> (<jats:italic>rs1045642<\/jats:italic>), and P\u2010gp function. P\u2010gp function (% \u0394MFI) was higher in White patients at troughs (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.031) compared to Black counterparts with similar trends at 4 and 8\u00a0h. Reduced AUC<jats:sub>0\u201312h<\/jats:sub> % \u0394MFI was noted in Black recipients (<jats:italic>N<\/jats:italic>\u00a0=\u00a032) compared with Whites (<jats:italic>N<\/jats:italic>\u00a0=\u00a035, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.029) with notable pairwise adjusted differences between Black and White women (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.021). Higher AUC<jats:sub>0\u201312h<\/jats:sub> % \u0394MFI was associated with <jats:italic>ABCB1 2677 TT<\/jats:italic> compared to <jats:italic>GG<\/jats:italic> variants (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.035). The AUC<jats:sub>0\u201312h<\/jats:sub> % \u0394MFI was greater in White than Black subjects. P\u2010gp function was higher at troughs in White subjects and differed between race\u2010sex groups. P\u2010gp function in PBMC may influence intracellular tacrolimus exposure and inter\u2010relating pharmacodynamic responses which may support race and sex pharmacologic differences.<\/jats:p>","DOI":"10.1111\/cts.13444","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T06:58:03Z","timestamp":1668063483000},"page":"184-192","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparison of P\u2010glycoprotein function in peripheral blood mononuclear cells ex vivo in stable Black and White male and female kidney transplant recipients"],"prefix":"10.1111","volume":"16","author":[{"given":"Kathleen M.","family":"Tornatore","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences University at Buffalo  Buffalo New York USA"},{"name":"Division of Nephrology and Transplantation, Department of Medicine, Erie County Medical Center, Jacobs School of Medicine and Biomedical Sciences University at Buffalo  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kris","family":"Attwood","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health University at Buffalo  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Brazeau","sequence":"additional","affiliation":[{"name":"Joan C. Edward School of Medicine Marshall University  Huntington West Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Sprowl","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences University at Buffalo  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirley","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Transplantation, Department of Medicine, Erie County Medical Center, Jacobs School of Medicine and Biomedical Sciences University at Buffalo  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aijaz","family":"Gundroo","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Transplantation, Department of Medicine, Erie County Medical Center, Jacobs School of Medicine and Biomedical Sciences University at Buffalo  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Minderman","sequence":"additional","affiliation":[{"name":"Flow and Image Cytometry Shared Resource Roswell Park Comprehensive Cancer Center  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rocco C.","family":"Venuto","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Transplantation, Department of Medicine, Erie County Medical Center, Jacobs School of Medicine and Biomedical Sciences University at Buffalo  Buffalo New York 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