Pharmacokinetics of clarithromycin in rats with acute renal failure induced by uranyl nitrate

Antimicrob Agents Chemother

et al. 2005

Self Cite

After intravenous and oral administration of clarithromycin at a dose of 20 mg/kg of body weight to rats with diabetes mellitus induced by alloxan (DMIA) and diabetes mellitus induced by streptozotocin (DMIS), the area under the curve values were significantly smaller than those of respective control rats. The in vitro intrinsic clearance values for the disappearance of clarithromycin were significantly faster in both rats with DMIA and rats with DMIS than in control rats. The above data suggested that metabolism of clarithromycin increased in both types of diabetic rat due to an increase in the expression and mRNA level of CYP3A1(23) in the rats.Animal models of insulin-dependent diabetes mellitus induced by administration of several chemicals, principally alloxan, streptozotocin, and zinc chelators, have been reported (22, 30). There are major differences in the diabetic effects of streptozotocin and alloxan (reference 30 and references therein). It is known that structural alterations in pancreatic beta cells (total degranulation) occur within 48 h after administration of streptozotocin and last up to 4 months. Alloxan causes a decrease in hepatic glycogen within 24 to 72 h, an effect that is partially reversible by insulin. Alloxan generally produces greater cytotoxicity owing to its conversion to anionic radicals.For rats with diabetes mellitus induced by streptozotocin (DMIS), a decreased bile flow rate and altered bile compositions (3), hepatotoxicity (31), and impaired kidney function (18, 21) have been reported. Glucuronidation and sulfation were also profoundly affected by DMIS in rats (23). In rats with diabetes mellitus induced by alloxan (DMIA), kidney function was also impaired (12,20).A previous study (13) has shown that the expression of hepatic microsomal cytochrome P450 (CYP) 1A2, 2B1/2, 2E1, and 3A23 increased 2.8, 1.8, 3.0, and 1.5 times, respectively, in rats with DMIA compared to controls, whereas the expression of CYP2C11 decreased to 23% of the control value. Similarly, the expression of CYP1A2, 2B1/2, 2E1, and 3A23 also increased 3.1, 3.3, 2.8, and 1.9 times, respectively, in rats with DMIS compared to controls, whereas the expression of CYP2C11 decreased to 37% of the control value. The mRNA levels of CYP1A2, 2B1, 2B2, 2E1, and 3A23 increased 3.4, 1.9, 1.6, 4.3, and 1.6 times, respectively, in rats with DMIA compared to controls, whereas CYP2C11 decreased to 31% of the control value. Similarly, the mRNA levels of CYP1A2, 2B1, 2B2, 2E1, and 3A23 also increased 4.2, 3.9, 1.9, 3.6, and 2.2 times, respectively, in rats with DMIS compared to controls, whereas CYP2C11 decreased to 28% of the control value. Similar changes in some of the above-mentioned CYP isozymes have also been reported for rats with DMIA and/or DMIS (8,15,(24)(25)(26)(27)32).It has been reported that CYP3A1 (23) is involved in the metabolism of clarithromycin in rats (14). Hence, it would be expected that pharmacokinetics of clarithromycin could be changed in rats with DMIA and DMIS due to an increase in the expression and...

mentioning

confidence: 99%

mentioning

confidence: 99%

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Effect of CYP3A1(23) Induction on Clarithromycin Pharmacokinetics in Rats with Diabetes Mellitus

Antimicrob Agents Chemother

et al. 2005

Self Cite

“…The numbers of male rats used were 8, 8 and 7 for control rats and rats pretreated with oxolamine at doses of 10 and 50 mg/kg, respectively, for phenytoin, and the corresponding values for torasemide and clarithromycin were 9, 10 and 10, and 8, 9 and 10. The blood sampling time schedules for phenytoin [11], torasemide [12] and clarithromycin [13] were the same as previously reported methods. The other procedures were similar to the above mentioned warfarin studies.…”

Section: Animalsmentioning

confidence: 99%

“…On day 4 just after oral administration of oxolamine, phenytoin (at a dose of 25 mg/kg; dissolved in distilled water with a minimum amount of 10 n NaOH), mainly metabolized via CYP2B1 in rats [11], torasemide (at a dose of 2.5 mg/kg; dissolved in distilled water with a minimum amount of 10 n NaOH and adjusted to a final pH of approximately 8 with Tris-HCl), mainly metabolized via CYP2C11 in rats [12], or clarithromycin (at a dose of 20 mg/kg; dissolved in 0.9% NaCl-injectable solution by adding few drops of 85% phosphoric acid), mainly metabolized via CYP3A2 in rats [13] was infused (total injection volume of 2 ml/kg for each drug) for 1 min via the jugular vein of male rats. The numbers of male rats used were 8, 8 and 7 for control rats and rats pretreated with oxolamine at doses of 10 and 50 mg/kg, respectively, for phenytoin, and the corresponding values for torasemide and clarithromycin were 9, 10 and 10, and 8, 9 and 10.…”

Section: Animalsmentioning

confidence: 99%

Gender difference in the pharmacokinetic interaction between oral warfarin and oxolamine in rats: inhibition of CYP2B1 by oxolamine in male rats

Zhu

Shin

2007

Biopharm & Drug Disp

The possible reason for the significantly greater AUC of oral warfarin with oral oxolamine in male Sprague-Dawley rats was evaluated. After oral administration of warfarin at a dose of 2 mg/kg to male rats with oxolamine at doses of 10 and 50 mg/kg, the AUC values of warfarin were significantly greater than the controls (254 and 330 versus 180 microg h/ml). However, the AUC values of warfarin were not affected by oxolamine in female rats. This could be due to inhibition of CYP2B1, 2C11 and 3A2 by oxolamine in male rats, since warfarin was metabolized via CYP1A1, 2B1, 2C6, 2C11 and 3A2 in rats and CYP2B1 is male dominant, and CYP2C11 and 3A2 are male specific. Therefore, phenytoin, torasemide and clarithromycin (mainly metabolized via CYP2B1/2, 2C11 and 3A2 in rats, respectively) were administered intravenously to male rats with or without oral oxolamine. After oral oxolamine at doses of 10 and 50 mg/kg, the AUC of phenytoin was significantly greater (1280 and 1640 versus 938 microg min/ml), however, the AUC values of torasemide and clarithromycin were independent of oxolamine. The above data suggest that the significantly greater AUC of oral warfarin with oral oxolamine could be due to inhibition of CYP2B1/2 by oxolamine in male rats.

Effects of acute renal failure on the pharmacokinetics of telithromycin in rats: negligible effects of increase in CYP3A1 on the metabolism of telithromycin

2007

Biopharm & Drug Disp

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It was reported that the expression of CYP3A1 increased in rats with acute renal failure induced by uranyl nitrate (rat model of U-ARF) compared with controls. It was shown that telithromycin was mainly metabolized via CYP3A1/2 in rats in this study. Hence, the pharmacokinetic parameters of telithromycin were compared after both intravenous and oral administration at a dose of 50 mg/kg to control rats and a rat model of U-ARF. After intravenous administration of telithromycin to rats with U-ARF, the AUC and renal clearance (Cl(r)) were significantly greater (35.0% increase) and slower (99.1% decrease), respectively, than the controls. Unexpectedly, the nonrenal clearance (Cl(nr)) of telithromycin was comparable between the two groups of rats, suggesting that CYP3A isozyme responsible for the metabolism of telithromycin seemed not to be expressed considerably in the rat model of U-ARF. After oral administration of telithromycin to rats with U-ARF, the AUC was also significantly greater (127% increase) than the controls and the value, 127%, was considerably greater than 35.0% after intravenous administration of telithromycin. This may be due mainly to the decrease in the intestinal first-pass effect of telithromycin compared with controls in addition to significantly slower Cl(r) than controls.