{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T04:23:53Z","timestamp":1778387033288,"version":"3.51.4"},"reference-count":15,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,3,7]],"date-time":"2013-03-07T00:00:00Z","timestamp":1362614400000},"content-version":"vor","delay-in-days":1740,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:p>Pegloticase is designed to convert urate into the easily excretable allantoin to treat hyperuricemia in gout. The aim of this analysis was to describe the pharmacokinetics and pharmacodynamics of pegloticase in 40 gout patients. Pegloticase was administered as intravenous infusions every 2 weeks at 4\u2010 and 8\u2010mg doses or every 4 weeks at 8\u2010 or 12\u2010mg doses for 12 weeks. Serum pegloticase concentrations, plasma urate, and serum antibody response were determined. Population pharmacokinetics and pharmacodynamics analyses were performed. Data were modeled simultaneously, and covariates were investigated (age, gender, race, body weight, ideal body weight, and antibody response). The dosing regimens to maintain uric acid levels below the therapeutic target of 6 mg\/dL were then predicted by the model. The pharmacokinetics were best described by a 1\u2010compartment linear model, while the pharmacodynamics model was fitted as a direct effect of pegloticase on uric acid concentrations with a suppressive maximum effect attributed to drug (E<jats:sub>max<\/jats:sub>) function. Pegloticase suppressed uric acid levels up to 83%. Weight only affected clearance and volume of distribution. No covariates affected pharmacodynamics. Simulation suggests pegloticase administered at 8 mg every 2 or 4 weeks as 2\u2010hour intravenous infusions will maintain uric acid levels well under 6 mg\/dL.<\/jats:p>","DOI":"10.1177\/0091270008317589","type":"journal-article","created":{"date-parts":[[2008,4,17]],"date-time":"2008-04-17T02:13:35Z","timestamp":1208398415000},"page":"708-718","source":"Crossref","is-referenced-by-count":25,"title":["Population Pharmacokinetic and Pharmacodynamic Analysis of Pegloticase in Subjects With Hyperuricemia and Treatment\u2010Failure Gout"],"prefix":"10.1002","volume":"48","author":[{"given":"Corinne Seng","family":"Yue","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Alton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan N.","family":"Maroli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Royce W.","family":"Waltrip","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Wright","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marika","family":"Di Marco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,3,7]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"2041","volume-title":"Arthritis and Allied Conditions","author":"Becker MA","year":"1997"},{"issue":"2","key":"e_1_2_6_3_2","first-page":"71","article-title":"A phase 2 study of multiple doses of intravenous poly(ethylene glycol) (PEG)\u2010uricase in patients with hyperuricemia and treatment\u2010failure gout","volume":"65","author":"Sundy JS","year":"2006","journal-title":"Ann Rheum Dis"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22403"},{"key":"e_1_2_6_5_2","volume-title":"ADAPT\u2010II Users Manual","author":"D'Argenio DZ","year":"1997"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.1996.113"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1023249510224"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2007.06.011"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1861"},{"issue":"9","key":"e_1_2_6_10_2","first-page":"S105","article-title":"Resolution of tophi with intravenous PEG\u2010uricase in refractory gout","volume":"52","author":"Baraf HSB","year":"2005","journal-title":"Arthritis Rheum"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1E259"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.3109\/03602538409015066"},{"key":"e_1_2_6_13_2","volume-title":"Pharmacokinetic & Pharmacodynamic Data Analysis: Concepts and Applications","author":"Gabrielsson J","year":"2007"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1033"},{"key":"e_1_2_6_15_2","volume-title":"Fasturtec [package insert]","year":"2007"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.4.83"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1177%2F0091270008317589","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1177\/0091270008317589","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T11:13:35Z","timestamp":1697109215000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1177\/0091270008317589"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,6]]},"references-count":15,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2008,6]]}},"alternative-id":["10.1177\/0091270008317589"],"URL":"https:\/\/doi.org\/10.1177\/0091270008317589","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,6]]}}}