Anatomical and physiological basis for the allometric scaling of cisplatin clearance in dogs
Autor: | Lara K. Maxwell, Satyanarayana Achanta, David W. A. Bourne, A. Sewell, K. Broaddus, J. W. Ritchey, Cyril R. Clarke |
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Rok vydání: | 2015 |
Předmět: |
Male
0301 basic medicine Aging Metabolic Clearance Rate Renal function Antineoplastic Agents Pharmacology Kidney urologic and male genital diseases Renal Circulation 03 medical and health sciences Dogs 0302 clinical medicine Pharmacokinetics medicine Animals General Veterinary business.industry Body Weight Reproducibility of Results Kidney metabolism Organ Size Effective renal plasma flow 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Renal blood flow Renal physiology Female Allometry Cisplatin business |
Zdroj: | Journal of Veterinary Pharmacology and Therapeutics. 39:224-236 |
ISSN: | 0140-7783 |
Popis: | Cisplatin is a platinum-containing cytotoxic drug indicated for the treatment of solid tumors in veterinary and human patients. Several of the algorithms used to standardize the doses of cytotoxic drugs utilize allometry, or the nonproportional relationships between anatomical and physiological variables, but the underlying basis for these relationships is poorly understood. The objective of this proof of concept study was to determine whether allometric equations explain the relationships between body weight, kidney weight, renal physiology, and clearance of a model, renally cleared anticancer agent in dogs. Postmortem body, kidney, and heart weights were collected from 364 dogs (127 juveniles and 237 adults, including 51 dogs ≥ 8 years of age). Renal physiological and cisplatin pharmacokinetic studies were conducted in ten intact male dogs including two juvenile and eight adult dogs (4-55 kg). Glomerular filtration rate (GFR), effective renal plasma flow, effective renal blood flow, renal cisplatin clearance, and total cisplatin clearance were allometrically related to body weight with powers of 0.75, 0.59, 0.61, 0.71, and 0.70, respectively. The similar values of these diverse mass exponents suggest a common underlying basis for the allometry of kidney size, renal physiology, and renal drug handling. |
Databáze: | OpenAIRE |
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