{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T02:02:03Z","timestamp":1760061723668},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T00:00:00Z","timestamp":1362700800000},"content-version":"vor","delay-in-days":3446,"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":[[2003,10]]},"abstract":"<jats:p>COL\u20103 is an oral, lipophilic, tetracycline analog that has been administered to patients with metastatic cancer. Preliminary assessment of COL\u20103 in 35 patients with refractory metastatic carcinoma demonstrated apparent nonlinear pharmacokinetics with highly variable oral clearance (63.9% coefficient of variance [CV]). To elucidate possible sources of variability of COL\u20103 pharmacokinetics in vivo, in vitro plasma protein binding and in vitro metabolism were explored along with in vivo pharmacokinetics using compartmental modeling. The variability in the overall clearance and urinary excretion of COL\u20103 was also assessed. COL\u20103 had a long terminal half\u2010life (median = 59.8 h), large apparent volume of distribution (median = 50.2 L), and low apparent clearance (median = 9.93 mL\/min). Only adjusted ideal body weight decreased the variability in total apparent clearance. There was nonsaturable plasma protein binding of COL\u20103 (f<jats:sub><jats:italic>u<\/jats:italic><\/jats:sub> = 5.5%), with the majority of binding to albumin. The renal route of elimination is negligible, with 0.06% of unchanged COL\u20103 and 3.31% COL\u20103 glucuronide excreted in the first 6 days. COL\u20103 is not metabolized by phase I metabolism but does undergo glucuronidation in vitro by UGT1A1, UGT1A3, UGT1A9, and UGT2B7 and in vivo, as evidenced by COL\u20103 glucuronides in the urine (median = 13.6% of the total dose). COL\u20103 exhibits nonlinear pharmacokinetics, possibly due to dissolution rate\u2010limited absorption.<\/jats:p>","DOI":"10.1177\/0091270003256675","type":"journal-article","created":{"date-parts":[[2003,9,26]],"date-time":"2003-09-26T19:47:23Z","timestamp":1064605643000},"page":"1124-1135","source":"Crossref","is-referenced-by-count":12,"title":["Factors Involved in the Pharmacokinetics of COL\u20103, a Matrix Metalloproteinase Inhibitor, in Patients with Refractory Metastatic Cancer: Clinical and Experimental Studies"],"prefix":"10.1002","volume":"43","author":[{"given":"Michelle 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