Anatomical and physiological basis for the allometric scaling of cisplatin clearance in dogs.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Achanta, S; Sewell, A; Ritchey, JW; Broaddus, K; Bourne, DWA; Clarke, CR; Maxwell, LK

Published Date

  • June 2016

Published In

Volume / Issue

  • 39 / 3

Start / End Page

  • 224 - 236

PubMed ID

  • 26440900

Pubmed Central ID

  • 26440900

Electronic International Standard Serial Number (EISSN)

  • 1365-2885

International Standard Serial Number (ISSN)

  • 0140-7783

Digital Object Identifier (DOI)

  • 10.1111/jvp.12266

Language

  • eng