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Tolerability and pharmacokinetic profile of a novel benzene‐poly‐carboxylic acids complex with cis‐diammineplatinum (II) dichloride in dogs with malignant mammary tumours
Authors:V. M. Kristiansen  S. Dewi  T. E. Horsberg  T. J. Jonasdottir  L. Moe  B. Berlinger  S. Lindkær‐Jensen  S. Larsen
Affiliation:1. Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway;2. Centre for Epidemiology and Biostatistics, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway;3. Department of Food Safety and Infection Biology, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway;4. Department of Chemical and Biological Work Environment, National Institute of Occupational Health, Oslo, Norway;5. Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College London, London, United Kingdom
Abstract:The pharmacokinetic profile, tolerability and efficacy of benzene‐poly‐carboxylic acids complex with cis‐diammineplatinum (II) dichloride (BP‐C1) were studied in dogs with mammary cancer. A three‐level response surface pathway designed trial was performed on seven dogs. At each level BP‐C1 was administered subcutaneously daily for 7 days followed by a 7‐day rest period in a dose escalating manner. Adverse events according to VCOG‐CTCAE, performance status and tumour progression were recorded. The pharmacokinetic profile followed a two‐compartment model with rapid absorption, short distribution, and a slow elimination phase. The overall elimination half‐life was 125 h. The maximum tolerated dose of BP‐C1 was estimated to be above 0.46 mg kg?1. A significant reduction in VCOG‐CTCAE toxicity which correlated negatively with increasing dose was found. The dogs' general performance status remained unchanged. No decrease in total tumour burden was found, although temporary tumour reduction was seen in some target tumours.
Keywords:BP‐C1  canine cancer  dose response  Immovet‐C8  mammary cancer  Response Surface Pathway (RSP) design
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