Pharmacokinetics of XXXX liposomes in @entity95 .

@entity1496 @entity16940 @entity95
PURPOSE: The dose-proportionality of pharmacokinetics of an iodinated contrast medium, @entity16940 , encapsulated into liposomes was investigated. METHODS: Following single intravenous administration of 150 mg @entity1496 /kg (potential diagnostic dose) and a five-fold higher dose in @entity95 the pattern of elimination was studied until 7 d and the blood concentrations were monitored up to 72 h after administration. The @entity1496 concentration in the liver was calculated on the basis of the blood concentration and related to the concentration measured in the @entity95 liver. RESULTS: The dose-normalized blood concentration-time profiles of the encapsulated @entity1496 were not superimposable. Contrary to the low dose a steady-state concentration of 2.8 mg @entity1496 /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 @entity1496 occurred predominantly via the kidneys and was complete 7 d after administration. The dose-normalized amounts of @entity1496 excreted with the urine were similar for both dose groups. From the blood data it was calculated that doses up to about 300 mg @entity1496 /kg should result in a dose-proportional increase of liposomal liver uptake before saturation occurs. This was confirmed by the measured @entity1496 liver concentrations after increasing the doses stepwise from 150 to 750 mg @entity1496 /kg. CONCLUSIONS: In @entity95 for the dose range 150 to 750 mg @entity1496 /kg @entity16940 liposomes reveal dose-dependent pharmacokinetics due to a saturation in liver uptake which occurs for doses of 300 mg @entity1496 /kg corresponding to 300 mg lipid/kg onwards.
