PHARMACOKINETICS OF IOPROMIDE LIPOSOMES IN RABBITS

The dose-proportionality of pharmacokinetics of an iodinated contrast medium, iopromide, encapsulated into liposomes was investigated. Metho ds. Following single intravenous administration of 150 mg iodine/kg (p otential diagnostic dose) and a five-fold higher dose in rabbits the p attern of elimination was studied until 7 d and the blood concentratio ns were monitored up to 72 h after administration. The iodine concentr ation in the liver was calculated on the basis of the blood concentrat ion and related to the concentration measured in the rabbit liver. Res ults. The dose-normalized blood concentration-time profiles of the enc apsulated iodine were not superimposable. Contrary to the low dose a s teady-state concentration of 2.8 mg iodine/ml was observed in blood fo r 60 min after the high dose administration indicating a saturation of the liposomal liver uptake. For both doses the elimination of iodine occurred predominantly via the kidneys and was complete 7 d after admi nistration. The dose-normalized amounts of iodine excreted with the ur ine were similar for both dose groups. From the blood data it was calc ulated that doses up to about 300 mg iodine/kg should result in a dose -proportional increase of liposomal liver uptake before saturation occ urs. This was confirmed by the measured iodine liver concentrations af ter increasing the doses stepwise from 150 to 750 mg iodine/kg. Conclu sions. In rabbits for the dose range 150 to 750 mg iodine/kg iopromide liposomes reveal dose-dependent pharmacokinetics due to a saturation in liver uptake which occurrs for doses of 300 mg iodine/kg correspond ing to 300 mg lipid/kg onwards.