{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T22:22:43Z","timestamp":1782858163011,"version":"3.54.5"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,3,7]],"date-time":"2013-03-07T00:00:00Z","timestamp":1362614400000},"content-version":"vor","delay-in-days":1041,"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":[[2010,5]]},"abstract":"<jats:p>Increased glucose flux through the polyol pathway and the resultant oxidative stress is thought to be a major mechanistic contributor to microvascular diabetic complications. Inhibition of flux through this pathway can be blocked through inhibition of either of 2 enzymes, aldose reductase (AR) or sorbitol dehydrogenase (SDH). This report describes the pharmacokinetics, biomarker pharmacodynamics, and safety of CP\u2010642,931, a potent and specific sorbitol dehydrogenase inhibitor (SDI). CP\u2010642,931 was administered for 7 days to 57 healthy volunteers in doses ranging from 1 to 35 mg daily. After the 35\u2010mg dose, CP\u2010642,931 showed a t<jats:sub>1\/2<\/jats:sub> of 20.1 hours and t<jats:sub>max<\/jats:sub> at 0.5 to 1.25 hours. After a 35\u2010mg dose, maximum inhibition of SDH was 91% (on days 1 and 7), and maximum serum sorbitol increase was 152\u2010fold on day 7 compared to control. Five participants discontinued the study due to adverse events, including myalgia, muscle spasm, and muscle fatigue. All symptoms resolved in all but 1 participant, who continued to report intermittent muscle fasciculations upon follow\u2010up. In conclusion, CP\u2010642,931 is a potent and specific SDI that is rapidly absorbed through the oral route and effectively inhibits SDH. However, the drug is not well tolerated due to adverse neuromuscular effects.<\/jats:p>","DOI":"10.1177\/0091270009336354","type":"journal-article","created":{"date-parts":[[2010,3,11]],"date-time":"2010-03-11T02:52:45Z","timestamp":1268275965000},"page":"521-530","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacokinetics, Pharmacodynamics, Tolerability, and Safety of a Novel Sorbitol Dehydrogenase Inhibitor in Healthy Participants"],"prefix":"10.1002","volume":"50","author":[{"given":"Zohar","family":"Landau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Novotny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory M.","family":"Preston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Freeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqing","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Oates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto A.","family":"Calle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,7]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.29.03.06.dc05-1254"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7742(02)50082-9"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.6.1615"},{"key":"e_1_2_5_5_2","volume-title":"Hyperglycemic Pseudohypoxia and Diabetes Complications: Sorbitol Pathway\u2010Generated NADHc Mediates Diabetes Complications","author":"Williamson JR","year":"2006"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.35.4.426"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2007.1630"},{"key":"e_1_2_5_8_2","first-page":"99","article-title":"Aldose reductase inhibitors: recent developments","volume":"40","author":"Sarges R","year":"1993","journal-title":"Prog Drug Res"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2004.12.018"},{"key":"e_1_2_5_10_2","first-page":"1032","article-title":"Sorbitol\u2010accumulating pyrimidine derivatives","volume":"44","author":"Geisen K","year":"1994","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.44.2.234"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm010440g"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001250050674"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051290"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199812000-00010"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.21.4.672"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diacomp.2004.04.003"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1056-8727(02)00169-1"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.3109\/13816818709031470"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03540350075038"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4347(91)80494-W"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867033457359"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.8.12.2095"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02584-6"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-9877(03)00013-6"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.2174\/138945008783431781"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(90)90032-8"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7742(02)50080-5"},{"issue":"2","key":"e_1_2_5_29_2","first-page":"151","article-title":"Sorbitol dehydrogenase deficiency in a family with congenital cataracts","volume":"7","author":"Shin YS","year":"1984","journal-title":"J Inherit Metab Dis"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00276598"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1177%2F0091270009336354","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1177\/0091270009336354","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T16:14:50Z","timestamp":1697472890000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1177\/0091270009336354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2010,5]]}},"alternative-id":["10.1177\/0091270009336354"],"URL":"https:\/\/doi.org\/10.1177\/0091270009336354","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,5]]}}}