|
|||||
|
|
Kidney and liver distribution of ochratoxin A in male and female F344 rats |
|
| Authors: | Ariane VettorazziIñaki Fernández de Trocóniz Elena González-PeñasLeire Arbillaga Laura-Ana CorcueraAna Gloria Gil Adela López de Cerain |
| Institution: | a Department of Nutrition and Food Sciences, Physiology and Toxicology, Faculty of Pharmacy, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain b Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain c Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain |
| Abstract: | The impact of age and gender on Ochratoxin A (OTA) distribution in kidney and liver were studied. OTA was quantified in kidney and liver of young and mature rats of both sexes. Data was fit simultaneously using the population approach with NONMEM program. Fed and fasted mature males showed a 30% decrease and an 11% increase in relative bioavailability, respectively, in comparison with the rest of the groups. The OTA concentrations reached in kidney and liver were very similar between both organs. The models that best fit to data were the ones that considered that distribution of OTA to kidney and liver occurs from the central compartment and that elimination occurs mainly from the liver compartment. The kinetic analysis revealed that both, the apparent volume of distribution of the central compartment (V/F) and the apparent volume of distribution of the liver and kidney compartments (VL,K/F) increased significantly with body weight. Thus, the sex differences observed in organs distribution are a reflection of the differences in relative bioavailability observed in adult males, as a consequence of the fed and fasted conditions and to the significant higher body weight of mature males which directly affected the V/F and VL,K/F. |
| Keywords: | AIC Akaike Information Criteria &minus 2LL &minus 2 × log (likelihood) BEN Balkan Endemic Nephropathy b w body weight CMAXobs maximum observed concentration CV(%) coefficient of variation CL/F apparent total plasma clearance F relative bioavailability F344 Fisher 344 rats HPLC-FLD high pressure liquid chromatography equipped with a fluorescence detector IAV inter-animal variability KA first order rate constant of absorption KC_L K first order rate constant of distribution from the central compartment to the liver and kidney compartments KL K_C first order rate constant of distribution from the liver and kidney compartments to the central compartment LOD limit of detection LOQ limit of quantification OTA ochratoxin A Q/F apparent distribution clearance TMAXobs time at maximum observed concentration V/F apparent volume of distribution of the central compartment VL K/F apparent volume of distribution of the liver and kidney compartments VT/F apparent volume of distribution of the peripheral compartment |
| 本文献已被 ScienceDirect 等数据库收录！ | |