RT Journal Article
SR Electronic
T1 Pharmacokinetics of iododoxorubicin in the rat, dog, and monkey.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 938
OP 945
VO 19
IS 5
A1 D M Edwards
A1 P Marrari
A1 C Efthymiopoulos
A1 G Basileo
A1 D Fraier
A1 E Pianezzola
A1 M Strolin-Benedetti
YR 1991
UL http://dmd.aspetjournals.org/content/19/5/938.abstract
AB The pharmacokinetics of iododoxorubicin (I-DOX) have been studied after single dose administration in the rat (iv and po), dog (iv and po), and monkey (iv). Plasma levels and amounts in urine were monitored by HPLC for both I-DOX and its biologically active metabolite, iododoxorubicinol (I-DOXOL). Plasma levels of I-DOX after iv administration could be described by a three-exponential curve with extremely fast initial phase. Terminal elimination half-lives of I-DOX were similar, 6-7 hr, in all three species. Body weight-normalized clearance (CL) and distribution volumes (Vd) of I-DOX were lower in the dog, but were similar in rat and monkey. The pharmacokinetic parameters also implied metabolic differences between species. Mean I-DOXOL/I-DOX AUC ratios were 0.02, 0.47, and 0.58, respectively, in rat, dog, and monkey, values considerably lower than reported in human studies. I-DOXOL remained slightly longer in the body than I-DOX, as seen both from terminal half-lives (9-11 hr) and mean residence times. In all species, renal excretion was virtually negligible: the amount of I-DOX + I-DOXOL in urine was less than 2% of dose. Mean bioavailabilities of I-DOX were 0.23 and 0.46 in rat and dog, respectively, and, in the latter, about half of I-DOXOL formation occurred during or before the first pass.