The largest contribution to total settlement occurred in the liver because it will be the primary organ for drug metabolic rate. It was also seen as a an extraction rate 2, even though the 200 mg/kg amount of 17GAC16Br in micelles resulted in better initial concentrations of 17GAOH in serum. 7 fold higher than free 17 DMAG at 10 mg/kg. The half Decitabine clinical trial life of the prodrug was only one, because a larger percentage of the prodrug was lost during its passage through the liver. 4 fold more than that of free 17 DMAG at 10 mg/kg regardless of its higher serum concentration. In Figure 4a, the data unveiled that free 17 DMAG at 10 mg/kg was eliminated through the urine at comparable levels to 17GAOH at 200 mg/kg. Curiously, their rates of urinary excretion were also similar despite the dose differences. Contrary to free 17 DMAG and 17GAOH, the micelles were eliminated slowly through the urine. The total renal clearance of free 17 DMAG is ca. Endosymbiotic theory 52 000 fold and 27 000 fold greater than the micelle formula at 10 and 200 mg/kg respectively. Taken together, at 10 mg/kg the full total clearance for 17GAC16Br in mPEG t PCL micelles decreased 11 fold-over free 17 DMAG, ultimately causing an important improvement in mean residence time for the lipophilic prodrug encapsulated in micelles and its hydrolyzed product 17GAOH. Taken together, the data suggest that the micellar system lowers non-specific systemic exposure through sustained release of 17GAOH. Considerable amounts of prodrugs were observed in all tissues assayed. The muscle collection was performed 3 h post i. v. In the 10 mg/kg quantity for that two formulations: free 17 DMAG in 0. 90-365 NaCl and 17GAC16Br in mPEG t PCL micelles. The tissue distribution timepoint was plumped for according to serum pharmacokinetic data for free 17 DMAG, that could still allow for accurate HPLC quantification of drug concentrations in all cells. The order of prodrug concentrations from highest to lowest at no cost 17 DMAG were: urinary bladder spleen lungs kidneys serum liver bone center muscle head. For 17GAC16Br in natural compound library mPEG w PCL micelles, the order from greatest concentration to cheapest was: spleen serum liver lungs muscle center bone help brain urinary bladder. For 17GAOH, the order from highest attention to lowest was: spleen urinary kidney liver help lungs heart bone muscle serum head. The tissue to serum ratio values in most tissues, except for brain and spleen, is consistent with the bigger volume of distribution and for the micellar formula was lower than free 17 DMAG frequently attributed to 17 DMAG. These differences in Kp prices could be related to the differences in partitioning and clearance between free 17 DMAG and the micelles.