{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:59:04Z","timestamp":1781053144435,"version":"3.54.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Aurinia Pharmaceuticals"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>An open-label phase 1 study was conducted to evaluate the effect of voclosporin following dosing with mycophenolate mofetil (MMF) on blood levels of mycophenolic acid (MPA, the active moiety of MMF) and MPA glucuronide (MPAG, the pharmacologically inactive metabolite of MMF) in subjects with systemic lupus erythematosus (SLE) and to assess the safety and tolerability of the combination.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>MMF was orally administered at a dose of 1\u2009g twice a day for at least 28\u2009days prior to the study and continued at the same dose throughout the study. Voclosporin was orally administered at a dose of 23.7\u2009mg twice a day for 7 consecutive days (Days 1\u20137), starting on the evening of Day 1 and ending with the morning dose on Day 7. Dense pharmacokinetic blood samples were collected pre-dose in the morning and from 0.25 to 12\u2009h after the morning doses. Analyses were derived by non-compartmental methods.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In 24 patients, MPA exposure [maximum serum concentration (Cmax) and area under the concentration curve from time 0 to 12 h (AUC0\u201312)] was similar in the presence and absence of voclosporin, with treatment ratios of 0.94 and 1.09, respectively [Cmax 16.5\u2009\u03bcg\/mL (Day 1) versus 15.8\u2009(Day 7), AUC0\u201312 39.1\u2009\u03bcg\/h\/mL (Day 1) versus 40.8 (Day 7)]. MPAG exposure showed a small increase in the presence of voclosporin (12% for Cmax and 27% for AUC0\u201312). Combination therapy was well tolerated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>There is no clinically meaningful interaction between voclosporin and MMF. As changes in exposure to MPA may affect efficacy and safety, these data confirm that voclosporin and MMF can be administered concomitantly without the need for dose adjustment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ndt\/gfab022","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T20:11:54Z","timestamp":1611951114000},"page":"917-922","source":"Crossref","is-referenced-by-count":20,"title":["Voclosporin: a novel calcineurin inhibitor with no impact on mycophenolic acid levels in patients with SLE"],"prefix":"10.1093","volume":"37","author":[{"given":"Teun","family":"van Gelder","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B","family":"Huizinga","sequence":"additional","affiliation":[{"name":"Aurinia Pharmaceuticals, Victoria, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Lisk","sequence":"additional","affiliation":[{"name":"Aurinia Pharmaceuticals, Victoria, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Solomons","sequence":"additional","affiliation":[{"name":"Aurinia Pharmaceuticals, Victoria, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,2,2]]},"reference":[{"key":"2022042423514589400_gfab022-B1","first-page":"330","article-title":"Manifestations of systemic lupus erythematosus","volume":"6","author":"Cojocaru","year":"2011","journal-title":"Maedica (Buchar)"},{"key":"2022042423514589400_gfab022-B2","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s11255-015-1201-z","article-title":"The effect of calcineurin inhibitors in the induction and maintenance treatment of lupus nephritis: a systematic review and meta-analysis","volume":"48","author":"Zhang","year":"2016","journal-title":"Int Urol Nephrol"},{"key":"2022042423514589400_gfab022-B3","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1136\/annrheumdis-2019-215089","article-title":"2019 update of the EULAR recommendations for the management of systemic lupus erythematosus","volume":"78","author":"Fanouriakis","year":"2019","journal-title":"Ann Rheum Dis"},{"key":"2022042423514589400_gfab022-B4","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1097\/FTD.0000000000000640","article-title":"Therapeutic drug monitoring of tacrolimus-personalized therapy: second consensus report","volume":"41","author":"Brunet","year":"2019","journal-title":"Ther Drug Monit"},{"key":"2022042423514589400_gfab022-B5","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/jcph.237","article-title":"Population PKPD of voclosporin in renal allograft patients","volume":"54","author":"Mayo","year":"2014","journal-title":"J Clin Pharmacol"},{"key":"2022042423514589400_gfab022-B6","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1093\/ndt\/gfw288","article-title":"Moderator\u2019s view: the use of calcineurin inhibitors in the treatment of lupus nephritis","volume":"31","author":"Kronbichler","year":"2016","journal-title":"Nephrol Dial Transplant"},{"key":"2022042423514589400_gfab022-B7","doi-asserted-by":"crossref","first-page":"2929","DOI":"10.1681\/ASN.2016040415","article-title":"Current and emerging therapies for lupus nephritis","volume":"27","author":"Parikh","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"2022042423514589400_gfab022-B8","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s13075-015-0621-6","article-title":"Comparison and evaluation of lupus nephritis response criteria in lupus activity indices and clinical trials","volume":"17","author":"Corapi","year":"2015","journal-title":"Arthritis Res Ther"},{"key":"2022042423514589400_gfab022-B9","doi-asserted-by":"crossref","first-page":"e000213","DOI":"10.1136\/lupus-2017-000213","article-title":"Early proteinuria response: a valid real-life situation predictor of long-term lupus renal outcome in an ethnically diverse group with severe biopsy-proven nephritis?","volume":"4","author":"Ugolini-Lopes","year":"2017","journal-title":"Lupus Sci Med"},{"key":"2022042423514589400_gfab022-B10","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/S0272-6386(00)70262-9","article-title":"Factors predictive of outcome in severe lupus nephritis","volume":"35","author":"Korbet","year":"2000","journal-title":"Am J Kidney Dis"},{"key":"2022042423514589400_gfab022-B11","doi-asserted-by":"crossref","first-page":"MO019","DOI":"10.1093\/ndt\/gfaa140.MO019","article-title":"Aurora phase 3 trial demonstrates voclosporin statistical superiority over standard of care in LN","volume":"35","author":"Caster","year":"2020","journal-title":"Nephrol Dial Transplant"},{"key":"2022042423514589400_gfab022-B12","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.kint.2018.08.025","article-title":"A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis","volume":"95","author":"Rovin","year":"2019","journal-title":"Kidney Int"},{"key":"2022042423514589400_gfab022-B13","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1093\/ndt\/14.3.706","article-title":"Mycophenolic acid plasma concentrations in kidney allograft recipients with or without cyclosporin: a cross-sectional study","volume":"14","author":"Gregoor","year":"1999","journal-title":"Nephrol Dial Transplant"},{"key":"2022042423514589400_gfab022-B14","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1097\/00007890-199911270-00028","article-title":"Effect of cyclosporine on mycophenolic acid trough levels in kidney transplant recipients","volume":"68","author":"Smak Gregoor","year":"1999","journal-title":"Transplantation"},{"key":"2022042423514589400_gfab022-B15","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1046\/j.1600-6143.2005.00779.x","article-title":"Cyclosporine interacts with mycophenolic acid by inhibiting the multidrug resistance-associated protein 2","volume":"5","author":"Hesselink","year":"2005","journal-title":"Am J Transplant"},{"key":"2022042423514589400_gfab022-B16","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/00007691-200104000-00005","article-title":"Comparison of the effects of tacrolimus and cyclosporine on the pharmacokinetics of mycophenolic acid","volume":"23","author":"van Gelder","year":"2001","journal-title":"Ther Drug Monit"},{"key":"2022042423514589400_gfab022-B17","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1038\/ki.2013.517","article-title":"Pharmacokinetic modeling of enterohepatic circulation of mycophenolic acid in renal transplant recipients","volume":"85","author":"Colom","year":"2014","journal-title":"Kidney Int"},{"key":"2022042423514589400_gfab022-B18","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2165\/00003088-200746010-00002","article-title":"Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients","volume":"46","author":"Staatz","year":"2007","journal-title":"Clin Pharmacokinet"},{"key":"2022042423514589400_gfab022-B19","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1111\/j.1600-6143.2005.01107.x","article-title":"Influence of co-medication with sirolimus or cyclosporine on mycophenolic acid pharmacokinetics in kidney transplantation","volume":"5","author":"Cattaneo","year":"2005","journal-title":"Am J Transplant"},{"key":"2022042423514589400_gfab022-B20","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jchromb.2008.08.023","article-title":"Development and validation of a LC\/MS\/MS method for quantifying the next generation calcineurin inhibitor, voclosporin, in human whole blood","volume":"874","author":"Handy","year":"2008","journal-title":"J Chromatogr B"},{"key":"2022042423514589400_gfab022-B21","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1111\/j.1600-6143.2011.03763.x","article-title":"The PROMISE study: a phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de novo kidney transplantation","volume":"11","author":"Busque","year":"2011","journal-title":"Am J Transplant"},{"key":"2022042423514589400_gfab022-B22","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/j.1399-0012.2006.00569.x","article-title":"Pharmacokinetics and variability of mycophenolic acid from enteric-coated mycophenolate sodium compared with mycophenolate mofetil in de novo heart transplant recipients","volume":"21","author":"Hummel","year":"2007","journal-title":"Clin Transplant"},{"key":"2022042423514589400_gfab022-B23","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/art.37795","article-title":"Epidemiology and sociodemographics of systemic lupus erythematosus and lupus nephritis among US adults with Medicaid coverage, 2000\u20132004","volume":"65","author":"Feldman","year":"2013","journal-title":"Arthritis Rheum"},{"key":"2022042423514589400_gfab022-B24","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/acr.21664","article-title":"American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis","volume":"64","author":"Hahn","year":"2012","journal-title":"Arthritis Care Res"}],"container-title":["Nephrology Dialysis Transplantation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ndt\/advance-article-pdf\/doi\/10.1093\/ndt\/gfab022\/36633770\/gfab022.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/article-pdf\/37\/5\/917\/43389835\/gfab022.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/article-pdf\/37\/5\/917\/43389835\/gfab022.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,24]],"date-time":"2022-04-24T23:52:07Z","timestamp":1650844327000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ndt\/article\/37\/5\/917\/6126039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,2]]},"references-count":24,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,2,2]]},"published-print":{"date-parts":[[2022,4,25]]}},"URL":"https:\/\/doi.org\/10.1093\/ndt\/gfab022","relation":{},"ISSN":["0931-0509","1460-2385"],"issn-type":[{"value":"0931-0509","type":"print"},{"value":"1460-2385","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,5]]},"published":{"date-parts":[[2021,2,2]]}}}