Pharmacokinetic changes of intravenous 2-(allylthio) pyrazine, a chemoprotective agent, in rats with acute renal failure induced by uranyl nitrate.
It was 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 (an inducer of CYP1A1/2 and 2E1 in rats) than that in control rats. It was also found that the CYP2E1 increased 2-4 times in rats with acute renal failure induced by uranyl nitrate (U-ARF) compared with those in control rats. Therefore, it could be expected that the pharmacokinetics of 2-AP could be changed in rats with U-ARF. After intravenous administration of 2-AP, 50 mg/kg, to rats with U-ARF, the area under the plasma concentration-time curve from time zero to time infinity (AUC) of 2-AP was significantly smaller (1030 versus 1360 microg min/ml) and this could be due to significantly faster CL of 2-AP (48.4 versus 36.8 ml/min/kg). This could be due to increased CYP2E1 in rats with U-ARF. More studies are required to find increased metabolite(s) of 2-AP in rats with U-ARF.
Lee
Eun J
EJ
College of Pharmacy and Research, Institute of Pharmaceutical Sciences, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, South Korea. leemg@snu.ac.kr
Kim
Eun J
EJ
Kim
Yoon G
YG
Chung
Hye C
HC
Kim
So H
SH
Kim
Dong H
DH
Lee
Inchul
I
Kim
Sang G
SG
Lee
Myung G
MG
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism*; D000418:Albumins / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D001806:Blood Urea Nitrogen; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D011719:Pyrazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014502:Uranyl Nitrate
C104935:2-(allylthio)pyrazine; D000418:Albumins; D004791:Enzyme Inhibitors; D011506:Proteins; D011719:Pyrazines; D014502:Uranyl Nitrate; D003404:Creatinine