The inter-species differences of estradiol metabolism were investigated in human, Beagle dog and rat liver microsomes by comparing enzyme kinetics of parent drug and the formation of its major metabolites. The incubation systems of estradiol with liver microsomes of the three species were optimized in terms of estradiol concentration, microsomal protein content and incubation time. The concentrations of estradiol and its metabolites were measured by LC-MS/MS method. The t1/2, CLint, CLh, Km and Vmax of estradiol incubated with male human liver microsomes were 40.02 +/- 8.32 min, 41.39 +/- 6.57 mL x min(-1) x kg(-1), 13.81 +/- 12.36 mL x min(-1) x kg(-1), 26.8 +/- 6.99 micromol x L(-1) and 0.75 +/- 0.92 micromol x L(-1) x min(-1), respectively. The corresponding parameters of female human were 44.71 +/- 10.21 min, 29.85 +/- 8.97 mL x min(-1) x kg(-1), 0.01 +/- 0.68 mL x min(-1) x kg(-1), 44.2 +/- 7.73 micromol x L(-1) and 1.27 +/- 4.41 micromol x L(-1) x min(-1), that of male dog were 21 +/- 7.33 min, 165.53 +/- 29.33 mL x min(-1) xkg(-1), 26.01 +/- 8.39 mL x min(-1) x kg(-1), 19.5 +/- 7.34 micromol x L(-1) and 1.6 +/- 0.65 micromol x L(-1) x min(-1), that of female dog were 25.5 +/- 5.32 min, 135.11 +/- 42.34 mL x min(-1) x kg(-1), 0.24 +/- 3.18 mL x min(-1) x kg(-1), 8.33 +/- 6.32 micromol x L(-1) and 0.51 +/- 2.15 micromol x L(-1) x min(-1), that of male rat were 5.11 +/- 3.84 min, 485.63 +/- 36.52 mL x min(-1) x kg(-1), 49.57 +/- 15.29 mL x min(-1) x kg(-1), 62 +/- 13.74 micromol x L(-1) and 19.16 +/- 9.67 micromol x L(-1) x min(-1), and that of female rat were 7.0 +/- 3.69 min, 354.82 +/- 33.33 mL x min(-1) x kg(-1), 8.04 +/- 3.23 mL x min(-1) x kg(-1), 35.38 +/- 7.65 micromol x L(-1) and 8.39 +/- 4.91 micromol x L(-1) min(-1), respectively. There were nine metabolites detected from all the three species, but the relative amounts of the metabolites generated were different in three species. The results indicted that the major phase I metabolic pathway of estradiol was similar in the liver microsomes from all the three species. However, the inter-species differences were found in the view of relative amounts of the metabolites as well as the metabolic characteristics of estradiol in liver microsomal incubation.

Objective To evaluate the reproducibility of normal liver ADC measurements by different respiratory motion compensation techniques. Methods A total of 31 young healthy volunteers who are 20 to 40 years old without any hepatic diseases were selected to research. Each volunteer underwent liver DWI twice in 24 hours with the same parameters and location. The imaging was performed with free-breath(FB), breathhold(BH), rspiratory-triggered(RT)and navigator-triggered(NT)techniques, and the ADC values of the left hepatic lobe and right hepatic lobe (upper, middle and lower) was acquired with two scans. Analysis the the ADC values of various anatomic locations of liver with two-way analysis of variance of randomized block design. Reproducibility of ADCs was assessed with the Bland-Altman method. Analysis of variance and paired-sample t test was used to assess ADCs from both right and left liver lobe among the four techniques. Result The ADC values acquired from the four techniques were significant differences (P<0.01),and the ADC values of the right lobe were less than the left lobe's(P<0.01). It showed a trend to decrease moving from superior to inferior levels in both left and right lobes, and the ADC values among The middle and lower were significant differences (P<0.01). The limit of agreement of ADC of twice imaging among the four techniques were as follow: the right lobe was less than the left lobes, and the breathhold was less the others. As the result, reproducibility in the right liver lobe was better to that in the left and the reproducibility with breathhold was better than the other respiratory motion compensation techniques. Conclusions Both anatomic location and DWI technique influence the liver ADC measurements and their reproducibility. The reproducibility of BH is the best.