Pharmacokinetic changes of drugs in rat model of acute renal failure induced by uranyl nitrate: correlation between drug metabolism and hepatic microsomal cytochrome P450 isozymes.
In male Sprague-Dawley rat model of acute renal failure induced by uranyl nitrate (rat model of U-ARF), the expression of CYP2C11 decreased by 20% of control, whereas that of CYP2E1 and 3A1(23) increased 2-4 and 4 times, respectively, as compared with controls. The expressions of CYPIA2 and 2B1/2 were not changed by U-ARF. The mRNA level of CYP2E1 increased 3 times and that of CYP2C11 decreased to 25% of controls. However, those of CYP1A2, 2B1, 2B2, and 3A2 were comparable to controls. These results of Northern blot analysis were consistent with those of Western blot analysis. Interestingly, however, the mRNA level of CYP3A23 did not increase in rat model of U-ARF. Hence, the induction of CYP3A23 expression by U-ARF may result from protein stabilization (i.e., a decrease in protein turnover). Hence, in this review, the changes in pharmacokinetics of drugs in rat model of U-ARF [especially the total area under the plasma concentration-time curve from time zero to time infinity (AUC) changes of metabolite(s)] reported from the literatures were tried to be explained in terms of CYP isozyme changes in rat model of U-ARF. Otherwise, the time-averaged nonrenal (Cl(nr)) or total body (Cl) clearance, or AUC of parent drugs were compared.
Lee
Myung Gull
MG
College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea. leemg@snu.ac.kr
Lee
Joo Hyun
JH
Oh
Jung Mi
JM
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004195:Disease Models, Animal; D007527:Isoenzymes / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014502:Uranyl Nitrate / Q000633:toxicity
D007527:Isoenzymes; D004364:Pharmaceutical Preparations; D014502:Uranyl Nitrate; D003577:Cytochrome P-450 Enzyme System