{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T06:35:27Z","timestamp":1776753327856,"version":"3.51.2"},"reference-count":18,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T00:00:00Z","timestamp":1362700800000},"content-version":"vor","delay-in-days":4846,"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":[[1999,12]]},"abstract":"<jats:p><jats:italic>The authors examined the pharmacokinetics of the CD 19 receptor\u2010directed tyrosine kinase inhibitor B43\u2010Genistein in 17 patients (4 children, 13 adults) with B\u2010lineage lymphoid malignancies, including 12 patients with acute lymphoblastic leukemia (ALL) and 5patients with non\u2010Hodgkin's lymphoma (NHL). The immune conjugate was administered intravenously as a 1\u2010hour continuous infusion at a dose level of either 0.1 mg\/kg (<\/jats:italic>N = <jats:italic>12) or 0.18 mg\/kg (<\/jats:italic>N = <jats:italic>5), and the plasma concentration\u2010time data were modeled by using the WinNonlin program to estimate the pharmacokinetic parameters. Pharmacokinetic analyses revealed a plasma half\u2010life of 19 \u00b1 4 hours, mean residence time of 22 \u00b1 4 hours, and a systemic clearance of 18 \u00b1 2 mL\/h\/kg. The average (mean \u00b1 SEM) values for the maximum plasma concentration C<jats:sub>max<\/jats:sub>, volume of distribution at steady state (V<jats:sub>ss<\/jats:sub>), and area under curve (AUC) were 1092 \u00b1 225ng\/ml, 291 \u00b1 37mL\/kg, and 9987 \u00b1 2021 \u03bcg \u00d7 h\/L, respectively The AUC values were higher at the 0.18 mg\/kg dose level than at the 0.1 mg\/kg dose level (16,848 \u00b1 5118 \u03bcg \u00d7 h\/L vs. 7128 \u00b1 1156 \u03bcg \u00d7 h\/L<\/jats:italic>, p = <jats:italic>0.009). Patients with ALL had a significantly larger volume of distribution at steady state (332 \u00b1 47 mL\/kg vs. 191 \u00b1 12 mL\/kg<\/jats:italic>, p = <jats:italic>0.04), faster clearance (21 \u00b1 3 mL\/h\/kg vs. 11 \u00b1 2 mL\/h\/kg<\/jats:italic>, p = <jats:italic>0.03), and lower dose\u2010corrected AUC than patients with NHL (6010 \u00b1 836 \u03bcg \u00d7 h\/L vs. 12,044 \u00b1 2707 \u03bcg \u00d7 h\/L<\/jats:italic>, p = <jats:italic>0.006). There was a trend toward faster clearance rates (23 \u00b1 4 mL\/h\/kg vs. 16 \u00b1 3 mL\/h\/kg<\/jats:italic>, p = <jats:italic>0.1), shorter elimination half\u2010lives (5.7 \u00b1 3.6 hours vs. 13 \u00b1 8.8 hours<\/jats:italic>, p = <jats:italic>0.1), and shorter mean residence times (11 \u00b1 3 hours vs. 25 \u00b1 5 hours<\/jats:italic>, p = <jats:italic>0.08) for non\u2010Caucasian patients as compared to Caucasian patients. When compared to adult patients, pediatric patients showed a significantly larger volume of distribution at steady state (418 \u00b1 82 mL\/kg vs. 252 \u00b1 34 mL\/kg<\/jats:italic>, p = <jats:italic>0.02) and a longer elimination half\u2010lives (18.4 \u00b1 13.6 hours vs. 8.7 \u00b1 6.7 hours<\/jats:italic>, p = <jats:italic>0.04). The pharmacokinetics of B43\u2010Genistein was not affected by the gender of the patients or by bone marrow transplantation in past medical history. Overall, B43\u2010Genistein showed favorable pharmacokinetics in this heavily pretreated leukemia\/lymphoma patient population, which is reminiscent of its recently reported favorable pharmacokinetics in cynomolgus monkeys. To our knowledge, this is the first clinical pharmacokinetics study of a tyrosine kinase inhibitor containing immunoconjugate<\/jats:italic>.<\/jats:p>","DOI":"10.1177\/00912709922012051","type":"journal-article","created":{"date-parts":[[2003,7,19]],"date-time":"2003-07-19T09:38:13Z","timestamp":1058607493000},"page":"1248-1255","source":"Crossref","is-referenced-by-count":19,"title":["Clinical Pharmacokinetics of the CD19 Receptor\u2010Directed Tyrosine Kinase Inhibitor B43\u2010Genistein in Patients with B\u2010Lineage Lymphoid Malignancies"],"prefix":"10.1002","volume":"39","author":[{"given":"Chun\u2010Lin","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Levine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asha","family":"Rao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"O'Neill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoav","family":"Messinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothea E.","family":"Myers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick","family":"Goldman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carole","family":"Hurvitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James T.","family":"Casper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatih M.","family":"Uckun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,3,8]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"crossref","first-page":"21172","DOI":"10.1016\/S0021-9258(19)36907-8","article-title":"Signal transduction through the CD19 receptor during discrete developmental stages of human B\u2010cell ontogeny","volume":"268","author":"Uckun 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