title: Anatomical and physiological basis for the allometric scaling of cisplatin clearance in dogs.
abstract: 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.
authors.affiliation: Departments of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, 74078, USA.
authors.forename: S
authors.initials: S
authors.lastname: Achanta
authors.affiliation: Departments of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, 74078, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sewell
authors.affiliation: Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, 74078, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Ritchey
authors.affiliation: Department of Veterinary Clinical Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, 74078, USA.
authors.forename: K
authors.initials: K
authors.lastname: Broaddus
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73117, USA.
authors.forename: D W A
authors.initials: DW
authors.lastname: Bourne
authors.affiliation: Departments of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, 74078, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Clarke
authors.affiliation: Departments of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, 74078, USA.
authors.forename: L K
authors.initials: LK
authors.lastname: Maxwell
mesh_terms: D000375:Aging; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001835:Body Weight; D002945:Cisplatin / Q000493:pharmacokinetics*; D004285:Dogs / Q000378:metabolism*; D005260:Female; D007668:Kidney / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology; D008297:Male; D008657:Metabolic Clearance Rate; D009929:Organ Size; D012079:Renal Circulation / Q000502:physiology; D015203:Reproducibility of Results
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin