Effects of acute renal failure induced by uranyl nitrate on the pharmacokinetics of 2-(allylthio) pyrazine, a chemoprotective agent, in rats: the role of CYP3A23 induction.
It has been reported that the total body clearance (CL) of 2-(allylthio)pyrazine (2-AP) was significantly faster after intravenous administration of 2-AP to rats pretreated with 3-methylcholanthrene, phenobarbital, and dexamethasone (main inducers of CYP1A1/2, CYP2B1/2, and CYP3A1/2, respectively, in rats) than those in respective control rats. It has also been reported that expression of CYP2E1 and CYP3A1(23) increased 2.3 and 4 times, respectively, in rats with acute renal failure induced by uranyl nitrate (U-ARF) compared with those in control rats. However, CYP1A2 and CYP2B1/2 expression was not changed. Therefore, it could be expected that the pharmacokinetics of 2-AP could be changed in rats with U-ARF due to increase in expression of CYP3A23 in the rats. After intravenous administration of 2-AP at a dose of 50 mg/kg to rats with U-ARF, the area under the plasma concentration-time curve from time zero to time infinity of 2-AP was significantly smaller (1030 versus 1360 microg min/ml) due to significantly faster CL of 2-AP (48.4 versus 36.8 ml/min/kg). This could be due to increased expression of CYP3A23 in rats with U-ARF.
Lee
Eun J
EJ
College of Pharmacy and Research Institute of Pharmaceutical Sciences, San 56-1, Shillim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
Kim
Eun J
EJ
Kim
Yoon G
YG
Chung
Hye C
HC
Kim
So H
SH
Kim
Dong H
DH
Lees
Inchul
I
Kim
Sang G
SG
Lee
Myung G
MG
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D000818:Animals; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D051544:Cytochrome P-450 CYP3A; D004790:Enzyme Induction / Q000187:drug effects; D007700:Kinetics; D008297:Male; D009942:Organometallic Compounds / Q000633:toxicity; D011719:Pyrazines / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
C104935:2-(allylthio)pyrazine; D009942:Organometallic Compounds; D011719:Pyrazines; C005460:uranyl acetate; D001189:Aryl Hydrocarbon Hydroxylases; C465138:Cyp3a23-3a1 protein, rat; D051544:Cytochrome P-450 CYP3A