@article {Balevice000811, author = {Stephen J Balevic and Rachel Randell and Daniel Weiner and Claire Beard and Laura Eve Schanberg and Christoph P Hornik and Michael Cohen-Wolkowiez and Daniel Gonzalez}, editor = {, and , and Abel, N and Abulaban, K and Adams, A and Adams, M and Agbayani, R and Aiello, J and Akoghlanian, S and Alejandro, C and Allenspach, E and Alperin, R and Alpizar, M and Amarilyo, G and Ambler, W and Anderson, E and Ardoin, S and Armendariz, S and Baker, E and Balboni, I and Balevic, S and Ballenger, L and Ballinger, S and Balmuri, N and Barbar-Smiley, F and Barillas-Arias, L and Basiaga, M and Baszis, K and Becker, M and Bell-Brunson, H and Beltz, E and Benham, H and Benseler, S and Bernal, W and Beukelman, T and Bigley, T and Binstadt, B and Black, C and Blakley, M and Bohnsack, J and Boland, J and Boneparth, A and Bowman, S and Bracaglia, C and Brooks, E and Brothers, M and Brown, A and Brunner, H and Buckley, M and Buckley, M and Bukulmez, H and Bullock, D and Cameron, B and Canna, S and Cannon, L and Carper, P and Cartwright, V and Cassidy, E and Cerracchio, L and Chalom, E and Chang, J and Chang-Hoftman, A and Chauhan, V and Chira, P and Chinn, T and Chundru, K and Clairman, H and Co, D and Confair, A and Conlon, H and Connor, R and Cooper, A and Cooper, J and Cooper, S and Correll, C and Corvalan, R and Costanzo, D and Cron, R and Curiel-Duran, L and Curington, T and Curry, M and Dalrymple, A and Davis, A and Davis, C and Davis, C and Davis, T and De Benedetti, F and De Ranieri, D and Dean, J and Dedeoglu, F and De Guzman, M and Delnay, N and Dempsey, V and DeSantis, E and Dickson, T and Dingle, J and Donaldson, B and Dorsey, E and Dover, S and Dowling, J and Drew, J and Driest, K and Du, Q and Duarte, K and Durkee, D and Duverger, E and Dvergsten, J and Eberhard, A and Eckert, M and Ede, K and Edelheit, B and Edens, C and Edens, C and Edgerly, Y and Elder, M and Ervin, B and Fadrhonc, S and Failing, C and Fair, D and Falcon, M and Favier, L and Federici, S and Feldman, B and Fennell, J and Ferguson, I and Ferguson, P and Ferreira, B and Ferrucho, R and Fields, K and Finkel, T and Fitzgerald, M and Fleming, C and Flynn, O and Fogel, L and Fox, E and Fox, M and Franco, L and Freeman, M and Fritz, K and Froese, S and Fuhlbrigge, R and Fuller, J and George, N and Gerhold, K and Gerstbacher, D and Gilbert, M and Gillispie-Taylor, M and Giverc, E and Godiwala, C and Goh, I and Goheer, H and Goldsmith, D and Gotschlich, E and Gotte, A and Gottlieb, B and Gracia, C and Graham, T and Grevich, S and Griffin, T and Griswold, J and Grom, A and Guevara, M and Guittar, P and Guzman, M and Hager, M and Hahn, T and Halyabar, O and Hammelev, E and Hance, M and Hanson, A and Harel, L and Haro, S and Harris, J and Harry, O and Hartigan, E and Hausmann, J and Hay, A and Hayward, K and Heiart, J and Hekl, K and Henderson, L and Henrickson, M and Hersh, A and Hickey, K and Hill, P and Hillyer, S and Hiraki, L and Hiskey, M and Hobday, P and Hoffart, C and Holland, M and Hollander, M and Hong, S and Horwitz, M and Hsu, J and Huber, A and Huggins, J and HuiYuen, J and Hung, C and Huntington, J and Huttenlocher, A and Ibarra, M and Imundo, L and Inman, C and Insalaco, A and Jackson, A and Jackson, S and James, K and Janow, G and Jaquith, J and Jared, S and Johnson, N and Jones, J and Jones, J and Jones, J and Jones, K and Jones, S and Joshi, S and Jung, L and Justice, C and Justiniano, A and Karan, N and Kaufman, K and Kemp, A and Kessler, E and Khalsa, U and Kienzle, B and Kim, S and Kimura, Y and Kingsbury, D and Kitcharoensakkul, M and Klausmeier, T and Klein, K and Klein-Gitelman, M and Kompelien, B and Kosikowski, A and Kovalick, L and Kracker, J and Kramer, S and Kremer, C and Lai, J and Lam, J and Lang, B and Lapidus, S and Lapin, B and Lasky, A and Latham, D and Lawson, E and Laxer, R and Lee, P and Lee, P and Lee, T and Lentini, L and Lerman, M and Levy, D and Li, S and Lieberman, S and Lim, L and Lin, C and Ling, N and Lingis, M and Lo, M and Lovell, D and Lowman, D and Luca, N and Lvovich, S and Madison, C and Madison, J and Magni Manzoni, S and Malla, B and Maller, J and Malloy, M and Mannion, M and Manos, C and Marques, L and Martyniuk, A and Mason, T and Mathus, S and McAllister, L and McCarthy, K and McConnell, K and McCormick, E and McCurdy, D and McCurdy Stokes, P and McGuire, S and McHale, I and McMonagle, A and McMullen-Jackson, C and Meidan, E and Mellins, E and Mendoza, E and Mercado, R and Merritt, A and Michalowski, L and Miettunen, P and Miller, M and Milojevic, D and Mirizio, E and Misajon, E and Mitchell, M and Modica, R and Mohan, S and Moore, K and Moorthy, L and Morgan, S and Morgan Dewitt, E and Moss, C and Moussa, T and Mruk, V and Murphy, A and Muscal, E and Nadler, R and Nahal, B and Nanda, K and Nasah, N and Nassi, L and Nativ, S and Natter, M and Neely, J and Nelson, B and Newhall, L and Ng, L and Nicholas, J and Nicolai, R and Nigrovic, P and Nocton, J and Nolan, B and Oberle, E and Obispo, B and O{\textquoteright}Brien, B and O{\textquoteright}Brien, T and Okeke, O and Oliver, M and Olson, J and O{\textquoteright}Neil, K and Onel, K and Orandi, A and Orlando, M and Osei-Onomah, S and Oz, R and Pagano, E and Paller, A and Pan, N and Panupattanapong, S and Pardeo, M and Paredes, J and Parsons, A and Patel, J and Pentakota, K and Pepmueller, P and Pfeiffer, T and Phillippi, K and Pires Marafon, D and Phillippi, K and Ponder, L and Pooni, R and Prahalad, S and Pratt, S and Protopapas, S and Puplava, B and Quach, J and Quinlan-Waters, M and Rabinovich, C and Radhakrishna, S and Rafko, J and Raisian, J and Rakestraw, A and Ramirez, C and Ramsay, E and Ramsey, S and Randell, R and Reed, A and Reed, A and Reed, A and Reid, H and Remmel, K and Repp, A and Reyes, A and Richmond, A and Riebschleger, M and Ringold, S and Riordan, M and Riskalla, M and Ritter, M and Rivas-Chacon, R and Robinson, A and Rodela, E and Rodriquez, M and Rojas, K and Ronis, T and Rosenkranz, M and Rosolowski, B and Rothermel, H and Rothman, D and Roth-Wojcicki, E and Rouster-Stevens, K and Rubinstein, T and Ruth, N and Saad, N and Sabbagh, S and Sacco, E and Sadun, R and Sandborg, C and Sanni, A and Santiago, L and Sarkissian, A and Savani, S and Scalzi, L and Schanberg, L and Scharnhorst, S and Schikler, K and Schlefman, A and Schmeling, H and Schmidt, K and Schmitt, E and Schneider, R and Schollaert-Fitch, K and Schulert, G and Seay, T and Seper, C and Shalen, J and Sheets, R and Shelly, A and Shenoi, S and Shergill, K and Shirley, J and Shishov, M and Shivers, C and Silverman, E and Singer, N and Sivaraman, V and Sletten, J and Smith, A and Smith, C and Smith, J and Smith, J and Smitherman, E and Soep, J and Son, M and Spence, S and Spiegel, L and Spitznagle, J and Sran, R and Srinivasalu, H and Stapp, H and Steigerwald, K and Sterba Rakovchik, Y and Stern, S and Stevens, A and Stevens, B and Stevenson, R and Stewart, K and Stingl, C and Stokes, J and Stoll, M and Stringer, E and Sule, S and Sumner, J and Sundel, R and Sutter, M and Syed, R and Syverson, G and Szymanski, A and Taber, S and Tal, R and Tambralli, A and Taneja, A and Tanner, T and Tapani, S and Tarshish, G and Tarvin, S and Tate, L and Taxter, A and Taylor, J and Terry, M and Tesher, M and Thatayatikom, A and Thomas, B and Tiffany, K and Ting, T and Tipp, A and Toib, D and Torok, K and Toruner, C and Tory, H and Toth, M and Tse, S and Tubwell, V and Twilt, M and Uriguen, S and Valcarcel, T and Van Mater, H and Vannoy, L and Varghese, C and Vasquez, N and Vazzana, K and Vehe, R and Veiga, K and Velez, J and Verbsky, J and Vilar, G and Volpe, N and von Scheven, E and Vora, S and Wagner, J and Wagner-Weiner, L and Wahezi, D and Waite, H and Walker, J and Walters, H and Wampler Muskardin, T and Waqar, L and Waterfield, M and Watson, M and Watts, A and Weiser, P and Weiss, J and Weiss, P and Wershba, E and White, A and Williams, C and Wise, A and Woo, J and Woolnough, L and Wright, T and Wu, E and Yalcindag, A and Yee, M and Yen, E and Yeung, R and Yomogida, K and Yu, Q and Zapata, R and Zartoshti, A and Zeft, A and Zeft, R and Zhang, Y and Zhao, Y and Zhu, A and Zic, C}, title = {Pharmacokinetics of hydroxychloroquine in paediatric lupus: data from a novel, direct-to-family clinical trial}, volume = {9}, number = {1}, elocation-id = {e000811}, year = {2022}, doi = {10.1136/lupus-2022-000811}, publisher = {Archives of Disease in childhood}, abstract = {Objective Determine the pharmacokinetics (PK) and exposure{\textendash}response of hydroxychloroquine (HCQ) and desethylhydroxychloroquine (DHCQ) in paediatric SLE (pSLE).Methods We conducted an exploratory phase 2, direct-to-family trial. Children enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry with a diagnosis of pSLE were eligible if they were receiving HCQ as standard of care for >=3 months. Biological samples were collected at up to four visits over a 6-month period. At each visit, plasma was obtained to measure the concentrations of HCQ and DHCQ, as well as cytokines. HCQ and DHCQ plasma PK data were analysed using a population PK modelling approach.Results Twenty-five subjects provided a total of 88 plasma concentrations for PK analysis. There was a poor linear fit between HCQ concentrations and total body weight (R2=0.03). There was a decline in both interferon (IFN)-alpha and IFN-gamma with higher concentrations of HCQ and DHCQ. Volume of distribution for HCQ in plasma was higher in children compared with published values in adults (73 000 L vs 44 000 L), but clearance values in children were similar to adults.Conclusions We report the first population PK model for HCQ and DHCQ in children using data from a novel direct-to-family clinical trial. We observed high interindividual variability in HCQ PK and found that weight-based dosing for HCQ is poorly correlated with drug concentrations, suggesting the need to use therapeutic drug monitoring to individualise dosing. Furthermore, our results suggest that the current weight-based dosing paradigm for HCQ may result in suboptimal drug exposures, particularly for children with obesity. Accordingly, additional studies of HCQ are needed in pSLE to determine the optimal drug concentration and dosing to reduce disease activity and improve outcomes.Trial registration number NCT04358302.No data are available.}, URL = {https://lupus.bmj.com/content/9/1/e000811}, eprint = {https://lupus.bmj.com/content/9/1/e000811.full.pdf}, journal = {Lupus Science \& Medicine} }