2-(allylthio)pyrazine and Acute-Kidney-Injury

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.

Topics: Acute Kidney Injury; Animals; Area Under Curve; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP3A; Enzyme Induction; Kinetics; Male; Organometallic Compounds; Pyrazines; Rats; Rats, Sprague-Dawley

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.

Topics: Acute Kidney Injury; Albumins; Animals; Area Under Curve; Blood Urea Nitrogen; Chromatography, High Pressure Liquid; Creatinine; Enzyme Inhibitors; Half-Life; Injections, Intravenous; Male; Organ Size; Proteins; Pyrazines; Rats; Rats, Sprague-Dawley; Uranyl Nitrate