Effect of hyperthermia on normal tissue toxicity and on adriamycin pharmacokinetics in dogs
Wilke, A.V.; Jenkins, C.; Milligan, A.J.; Legendre, A.; Frazier, D.L.
Cancer Research 51(6): 1680-1683
1991
ISSN/ISBN: 0008-5472 PMID: 1671828 Document Number: 383739
This study examined the effects of Adriamycin (ADR) (30 mg/m2), whole-body hyperthermia (WBH) (42.degree.C for 1 h), and the combination of the two (ADR plus WBH) on gastrointestinal and hematopoietic toxicity and the effects of WBH on ADR pharmacokinetics in the normal dog (n = 5/treatment group). Duodenal biopsies were collected from animals in each group via endoscopy and were incubated in the presence of [3H]thymidine as an index of cell turnover. Additional duodenal biopsies were assayed for the enzymes .gamma.-glutamyltranspeptidase, N-acetyl-.beta.-D-glucosaminidase, and succinate dehydrogenase. Complete blood chemistry profiles and differential blood cell counts were done prior to and following treatment. Cell turnover was most depressed 3 days after ADR or ADR plus WBH; WBH alone had little effect on cell turnover. Neither .gamma.-glutamyltranspeptidase, N-acetyl-.beta.-D-glucosaminidase, nor succinate dehydrogenase activities were significantly altered by any of the treatment protocols. High performance liquid chromatography was used to quantify Adriamycin and adriamycinol in samples collected up to 6 h after drug administration. Duodenal biopsies were collected immediately and 1 h after drug administration for measurement of tissue concentrations of Adriamycin. A significant increase in the apparent volume of distribution and whole-body clearance and decrease in area under the plasma Adriamycin concentration versus time curve occurred when drug was administered concurrently with WBH. This differs from results reported in some other mammalian species.