Pharmacokinetics of paclitaxel in experimental animals. Part 2. Tissue distribution

: In S 180 bearing male mice, paclitaxel was rapidly distributed to various tissues within 10 minutes. The highest AUC was seen in the liver, and relatively high in the pancreas, kidney, thymus, intestine, stomach and lung. The concentration of paclitaxel in tumor tissue was not so high early time after administration, but was sustained for a long time with a half life of 12.3 hr. Elimination from the testis and thymus was also slow. The drug level in the brain was very low. In M 109 bearing female CDF1 mice, the distribution and elimination profile of paclitaxel was comparable to that in S 180 mice. The concentration of paclitaxel in the ovary, lung and uterus decreased slowly. In M 109 tumor, which was very sensitive to paclitaxel, the drug had a higher and long lasting distribution compared with S 180 tumor. In S 180 tumor bearing mice pretreated with CCl4, the paclitaxel level was found to be lower in the liver and higher in the other tissues including tumor, plasma, urine and bile than in non-treated mice.