Pharmacokinetics of iopromide liposomes in rabbits.
OBJECTIVE
The dose-proportionality of pharmacokinetics of an iodinated contrast medium, iopromide, encapsulated into liposomes was investigated.


METHODS
Following single intravenous administration of 150 mg iodine/kg (potential diagnostic dose) and a five-fold higher dose in rabbits the pattern of elimination was studied until 7 d and the blood concentrations were monitored up to 72 h after administration. The iodine concentration in the liver was calculated on the basis of the blood concentration and related to the concentration measured in the rabbit liver.


RESULTS
The dose-normalized blood concentration-time profiles of the encapsulated iodine were not superimposable. Contrary to the low dose a steady-state concentration of 2.8 mg iodine/mL was observed in blood for 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 administration. The dose-normalized amounts of iodine excreted with the urine were similar for both dose groups. From the blood data it was calculated that doses up to about 300 mg iodine/kg should result in a dose-proportional increase of liposomal liver uptake before saturation occurs. This was confirmed by the measured iodine liver concentrations after increasing the doses stepwise from 150 to 750 mg iodine/kg.


CONCLUSIONS
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 occurs for doses of 300 mg iodine/kg corresponding to 300 mg lipid/kg onwards.
D000818:Animals; D002214:Capsules; D003287:Contrast Media / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007275:Injections, Intravenous; D007455:Iodine / Q000097:blood; D007472:Iohexol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D011817:Rabbits
D002214:Capsules; D003287:Contrast Media; D008081:Liposomes; D007472:Iohexol; C038192:iopromide; D007455:Iodine