Comparable efficacy of oral bendamustine versus intravenous administration in treating hematologic malignancies.

Autor: Cracchiolo MJ; Department of Pediatrics, University of Arizona, 1501 N. Campbell Ave., PO Box 245073, Tucson, AZ, 85724-5073, USA., Davis L; R. Ken Coit College of Pharmacy, University of Arizona, Tucson, AZ, USA., Matiatos AP; Department of Pediatrics, University of Arizona, 1501 N. Campbell Ave., PO Box 245073, Tucson, AZ, 85724-5073, USA., Davini DW; Department of Pediatrics, University of Arizona, 1501 N. Campbell Ave., PO Box 245073, Tucson, AZ, 85724-5073, USA., Husnain M; Department of Medicine, University of Arizona, Tucson, AZ, USA.; The University of Arizona Cancer Center, Tucson, AZ, USA., Simpson RJ; Department of Pediatrics, University of Arizona, 1501 N. Campbell Ave., PO Box 245073, Tucson, AZ, 85724-5073, USA.; Department of Immunobiology, University of Arizona, Tucson, AZ, USA.; School of Nutritional Sciences and Wellness, University of Arizona, Tucson, AZ, USA.; The University of Arizona Cancer Center, Tucson, AZ, USA., Voudouris V; Exinda Therapeutics LLC, El Dorado Hills, CA, USA., Katsanis E; Department of Pediatrics, University of Arizona, 1501 N. Campbell Ave., PO Box 245073, Tucson, AZ, 85724-5073, USA. ekatsani@arizona.edu.; Department of Immunobiology, University of Arizona, Tucson, AZ, USA. ekatsani@arizona.edu.; Department of Medicine, University of Arizona, Tucson, AZ, USA. ekatsani@arizona.edu.; Department of Pathology, University of Arizona, Tucson, AZ, USA. ekatsani@arizona.edu.; The University of Arizona Cancer Center, Tucson, AZ, USA. ekatsani@arizona.edu.
Jazyk: angličtina
Zdroj: Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2024 Sep; Vol. 94 (3), pp. 361-372. Date of Electronic Publication: 2024 Jun 15.
DOI: 10.1007/s00280-024-04688-y
Abstrakt: Purpose: The purpose of this study was to analyze potential differences in antitumor efficacy and pharmacokinetics between intravenous (IV) bendamustine and a novel orally administered (PO) bendamustine agent that is utilizing the beneficial properties of superstaturated solid dispersions formulated in nanoparticles.
Methods: Pharmacokinetics of IV versus PO bendamustine were determined by analysis of plasma samples collected from NSG mice treated with either IV or PO bendamustine. Plasma samples were analyzed using liquid chromatography-mass spectrometry following a liquid-liquid extraction to determine peak bendamustine concentration, area under the concentration-time curve, and the half-life in-vivo. In-vitro cytotoxicity of bendamustine against human non-Hodgkin Burkitt's Lymphoma (Raji), multiple myeloma (MM.1s), and B-cell acute lymphoblastic leukemia (RS4;11) cell lines was determined over time using MTS assays. Luciferase-tagged versions of the aforementioned cell lines were used to determine in-vivo bendamustine cytotoxicity of IV versus PO bendamustine at two different doses.
Results: Bendamustine at a high dose in-vitro causes cell death. There was no significant difference in antitumor activity between IV and novel PO bendamustine at a physiologically relevant concentration in all three xenograft models. In-vivo pharmacokinetics showed the oral bioavailability of bendamustine in mice to be 51.4%.
Conclusions: The novel oral bendamustine agent tested exhibits good oral bioavailability and systemic exposure for in-vivo antitumor efficacy comparable to IV bendamustine. An oral bendamustine formulation offers exciting clinical potential as an additional method of administration for bendamustine and warrants further evaluation in clinical studies.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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