Cancer Chemother Pharmacol DOI 10.1007/s00280-015-2727-6
ORIGINAL ARTICLE
Pharmacokinetic and pharmacodynamic profile of bendamustine and its metabolites Mona Darwish1 · Mary Bond2 · Edward Hellriegel3 · Philmore Robertson Jr.3 · James P. Chovan3
Received: 23 December 2014 / Accepted: 15 March 2015 © The Author(s) 2015. This article is published with open access at Springerlink.com
Abstract Purpose Bendamustine is a unique alkylating agent indicated for the treatment of chronic lymphocytic leukemia and rituximab-refractory, indolent B cell non-Hodgkin’s lymphoma. Despite the extensive experience with bendamustine, its pharmacokinetic profile has only recently been described. This overview summarizes the pharmacokinetics, pharmacokinetic/pharmacodynamic relationships, and drug–drug interactions of bendamustine in adult and pediatric patients with hematologic malignancies. Methods A literature search and data on file (including a human mass balance study, pharmacokinetic population analyses in adult and pediatric patients, and modeling analyses) were evaluated for inclusion. Results Bendamustine concentrations peak at end of intravenous infusion (~1 h). Subsequent elimination is triphasic, with the intermediate t1/2 (~40 min) as the effective t1/2 since the final phase represents
ORIGINAL ARTICLE
Pharmacokinetic and pharmacodynamic profile of bendamustine and its metabolites Mona Darwish1 · Mary Bond2 · Edward Hellriegel3 · Philmore Robertson Jr.3 · James P. Chovan3
Received: 23 December 2014 / Accepted: 15 March 2015 © The Author(s) 2015. This article is published with open access at Springerlink.com
Abstract Purpose Bendamustine is a unique alkylating agent indicated for the treatment of chronic lymphocytic leukemia and rituximab-refractory, indolent B cell non-Hodgkin’s lymphoma. Despite the extensive experience with bendamustine, its pharmacokinetic profile has only recently been described. This overview summarizes the pharmacokinetics, pharmacokinetic/pharmacodynamic relationships, and drug–drug interactions of bendamustine in adult and pediatric patients with hematologic malignancies. Methods A literature search and data on file (including a human mass balance study, pharmacokinetic population analyses in adult and pediatric patients, and modeling analyses) were evaluated for inclusion. Results Bendamustine concentrations peak at end of intravenous infusion (~1 h). Subsequent elimination is triphasic, with the intermediate t1/2 (~40 min) as the effective t1/2 since the final phase represents
