October 26, 2010
Bendamustine PK and PK/PD Study Published
Results of a population pharmacokinetic and exposure-reponse analysis of bendamustine were published in the November 2010 issue of Cancer Chemotherapy and Pharmacology.
Following a single dose of bendamustine HCl, concentrations declined in a triphasic manner, with rapid distribution, intermediate, and slow terminal phases. Bendamustine pharmacokinetics were not affected by age, sex, mild or moderate renal impairment, or mild liver impairment. No correlation was observed between exposure and most safety or efficacy measures because of the limited range of exposures after 120 mg/m2 administration. However, bendamustine Cmax was a significant (P=0.013) predictor of the probability of nausea in patients, most of whom were pretreated with antiemetics. The study demonstrated that the body surface area-based dosing regimen for bendamustine achieved the targeted exposure and was associated with a high incidence of therapeutic response.
Bendamustine (Treanda) is a novel chemotherapeutic agent composed of a bifunctional mechlorethamine alkylating group, a purinelike benzimidazole ring, and a butyric acid side chain. The study was sponsored by Cephalon, Inc., in collaboration with Cognigen Corporation and the University of Wisconsin School of Medicine and Public Health.
Owen JS, Melhem M, Passarell JA, D’Andrea D, Darwish M, Kahl B. Bendamustine pharmacokinetic profile and exposure–response relationships in patients with indolent non-Hodgkin’s lymphoma. Cancer Chemother Pharmacol 2010:66(6):1039-1049. doi:10.1007/s00280-010-1254-8
