Renal irradiation and the pharmacology and toxicity of methotrexate and cisplatinum. Int J Radiat Oncol Biol Phys 1986 Aug;12(8):1415-8
Date
08/01/1986Pubmed ID
3759566DOI
10.1016/0360-3016(86)90184-7Scopus ID
2-s2.0-0022447901 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
We used a rat model to study the effects of renal irradiation on the pharmacology of methotrexate (MTX) and cisplatinum (cis-Pt). Unanesthetized rats were given bilateral kidney irradiation (20 Gy in 9 fractions). At 9 months after irradiation, 3% of the animals had died and survivors showed moderately impaired renal function. At 15 months, 30% of the animals had died and survivors showed severely impaired renal function. Some animals were given i.v. MTX 1 week to 15 months after irradiation. In irradiated rats, the area under the MTX plasma clearance curve equaled that of controls through 6 months, and was significantly above controls from 9 months on. Other animals were given i.p. cis-Pt 1 week to 9 months after irradiation. The acute toxicity of cis-Pt was the same in control and irradiated rats when cis-Pt was given immediately before or after irradiation. Beginning 3 months after irradiation there was a progressive increase in cis-Pt toxicity and a simultaneous decrease in urinary platinum excretion. Irradiated animals that survived cis-Pt treatment showed increased radiation nephritis; the greatest effect occurred when cis-Pt was given 3 months or more after irradiation. MTX and cis-Pt clearance decreased when renal dysfunction was first observed and changes in renal function preceded changes in drug clearance and toxicity.
Author List
Moulder JE, Holcenberg JS, Kamen BA, Cheng M, Fish BLMESH terms used to index this publication - Major topics in bold
AnimalsCisplatin
Kidney
Methotrexate
Radiation Injuries, Experimental
Rats