title: Enhanced renal clearance of vancomycin in rats with carcinogen-induced osteosarcoma.
abstract: Recently, it has been reported that total clearance (CLtot) of vancomycin is significantly higher in patients with malignancies compared to those without malignancies. In the present study, to clarify the mechanism of this enhancement in malignancy, we adopted rat animal models, using chemical carcinogen-induced osteosarcoma, selected lung metastatic lesions (C-SLM), transplanted into thigh muscles. The CLtot and renal clearance (CLr) of vancomycin in the tumor-bearing rats were increased compared to the ones of the control rats without tumor. However, there was no difference in the glomerular filtration rate. The plasma concentrations of interleukin (IL)-1β and IL-6, were elevated in the tumor-bearing rats. When renal proximal tubular epithelial cells (RPTEC) were exposed to IL-1β, IL-6, and tumor necrosis factor (TNF)-α simultaneously, the excretory ratio increased significantly. These findings suggest that tubular excretion or re-absorption by cytokines might be associated with changes in the vancomycin CLtot enhancement in the tumor-bearing rats.
authors.affiliation: Department of Pharmacy, National Hospital Organization Kanazawa Medical Center, Kanazawa, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Shimada
authors.forename: Chieko
authors.initials: C
authors.lastname: Iwata
authors.forename: Shino
authors.initials: S
authors.lastname: Taga
authors.forename: Hitomi
authors.initials: H
authors.lastname: Teramachi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nomura
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuciya
authors.forename: Takashi
authors.initials: T
authors.lastname: Wada
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kimura
authors.forename: Ryo
authors.initials: R
authors.lastname: Matsushita
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002273:Carcinogens / Q000633:toxicity*; D007668:Kidney / Q000378:metabolism*; D023421:Models, Animal; D012516:Osteosarcoma / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D014640:Vancomycin / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D002273:Carcinogens; D014640:Vancomycin