Because it will be the principal organ for drug metabolism the largest contribution to total settlement occurred in the liver. Even though the 200 mg/kg amount of 17GAC16Br in micelles led to better initial levels of 17GAOH in serum, it was also characterized by an extraction ratio 2. 7 fold greater than free 17 DMAG at 10 mg/kg. The half Lu AA21004 life of the prodrug was just one, because a larger percentage of the prodrug was lost during its passage through the liver. 4 fold greater than that of free 17 DMAG at 10 mg/kg notwithstanding its higher serum concentration. In Figure 4a, the data unmasked that free 17 DMAG at 10 mg/kg was cleared through the urine at comparable levels to 17GAOH at 200 mg/kg. Apparently, their rates of urinary excretion were also similar regardless of the dosage differences. In contrast to free 17 DMAG and 17GAOH, the micelles were removed slowly through the urine. The total renal clearance of free 17 DMAG is ca. Immune system 52 000 fold and 27 000 fold more than the micelle formulation at 200 and 10 mg/kg respectively. Taken together, at 10 mg/kg the sum total clearance for 17GAC16Br in mPEG t PCL micelles lowered 11 fold over free 17 DMAG, resulting in a substantial improvement in mean residence time for the prodrug encapsulated in micelles and its hydrolyzed solution 17GAOH. Taken together, the data suggest the micellar system decreases non specific endemic coverage through release of 17GAOH. Quantifiable amounts of prodrugs were observed in all tissues assayed. The tissue series was performed 3 h post i. v. at the 10 mg/kg dose for the two formulations: free 17 DMAG in 0. 9% NaCl and 17GAC16Br in mPEG w PCL micelles. The tissue distribution timepoint was chosen depending on serum pharmacokinetic data for free 17 DMAG, that could still allow for precise HPLC quantification of drug concentrations in all cells. The order of prodrug concentrations from highest to lowest for free 17 DMAG were: urinary bladder spleen lungs kidneys serum liver bone center muscle brain. For 17GAC16Br in PFT alpha mPEG b PCL micelles, the order from highest concentration to cheapest was: spleen serum liver lungs muscle center bone elimination head urinary bladder. For 17GAOH, the order from concentration to lowest was: spleen urinary bladder liver kidney lungs heart bone muscle serum mind. The tissue to serum ratio values in every cells, except for spleen and mind, for the micellar method was below free 17 DMAG and is consistent with the much larger level of distribution generally related to 17 DMAG. These differences in Kp beliefs might be ascribed to the differences in partitioning and settlement between free 17 DMAG and the micelles.