PHARMACOKINETICS AND TISSUE DISTRIBUTION OF CISPLATIN IN NUDE-MICE - PLATINUM LEVELS AND CISPLATIN DNA-ADDUCTS

Citation
A. Johnsson et al., PHARMACOKINETICS AND TISSUE DISTRIBUTION OF CISPLATIN IN NUDE-MICE - PLATINUM LEVELS AND CISPLATIN DNA-ADDUCTS, Cancer chemotherapy and pharmacology, 37(1-2), 1995, pp. 23-31
Citations number
43
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Pharmacy",Oncology
ISSN journal
0344-5704
Volume
37
Issue
1-2
Year of publication
1995
Pages
23 - 31
Database
ISI
SICI code
0344-5704(1995)37:1-2<23:PATDOC>2.0.ZU;2-Y
Abstract
The pharmacokinetics of platinum (Pt) and cisplatin (CDDP)-DNA adducts were studied in nude mice after single-dose CDDP treatments. Whole bl ood, serum, kidney, lever, testis, brain, and tumor were collected at different intervals after injection of CDP at different dose levels. P t was measured with flameless atomic absorption spectrometry (FAAS) or adsorptive voltammetry (AdV) and CDDP-DNA adducts with quantitative i mmunohistochemistry. The drug was immediately absorbed into the blood circulation (peak serum Pt levels were reached within 5 min) after i.p . CDDP administration, and distribution into most tissues also occurre d rapidly (tissue Pt levels peaked at 15 min). With a sampling period of 7 days there was a biphasic elimination of Pt from blood, serum, an d tissues. In the brain the pharmacokinetics differed with a gradual a ccumulation of Pt occurring during the Ist week. Formation of CDDP-DNA adducts in tissues was a slower process, with maximal levels being ac hieved at between 30 min and 4 h after drug administration, followed b y a steady state lasting for at least 24 h. Each tissue type had its s pecific immunohistochemical staining pattern of adducts. With escalati ng CDDP doses there was a linear, or almost linear, increase in Pt con centrations and CDDP-DNA adduct levels in all sample types examined. T hese results suggest that a fair estimation of the amount of drug in t umor and normal tissues can be made from analysis of serum Pt at a fix ed time point after a single dose of CDDP.