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
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.