Effects of recombinant human growth hormone on the pharmacokinetics of intravenous chlorzoxazone in rats with acute renal failure induced by uranyl nitrate

Kwon

et al. 2004

Biopharm & Drug Disp

In rats pretreated with dexamethasone (an inducer of CYP3A1/2 in rats) and troleandomycin (an inhibitor of CYP3A1/2 in rats), the area under the plasma concentration-time curve from time zero to time infinity (AUC) values of clarithromycin were significantly smaller (365 compared with 600 micro g min/ml) and greater (1410 compared with 581 micro g min/ml), respectively, than those in control rats. This indicated that clarithromycin was metabolized via CYP3A1/2 in rats. The expression of CYP3A1(23) increased in rats with acute renal failure induced by uranyl nitrate (rats with U-ARF). Hence, it could be expected that AUC of clarithromycin could be smaller in rats with U-ARF. However, after intravenous administration of clarithromycin at a dose of 20mg/kg, the AUC and time-averaged total body (Cl) and nonrenal (Cl(nr)) clearance values were comparable between the two groups of rats. The 9000 x g supernatant fraction of liver homogenates in rats with U-ARF had comparable metabolic activities for clarithromycin compared with those in control rats, suggesting that the CYP3A isozyme responsible for metabolism of clarithromycin seemed not to be expressed considerably in the rats. This could explain the comparable AUC, Cl and Cl(nr) values of clarithromycin between the two groups of rats.

Section: Introductionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 92%

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

Kwon

et al. 2004

Biopharm & Drug Disp

“…CZX, once used as a skeletal muscle relaxant for the treatment of painful muscle spasms (Chen and Yang, 1996), primarily undergoes hydroxylation to form 6-hydroxychlorzoxazone (6-OHCZX), which is primarily catalyzed via CYP2E1 in humans (Coney and Burns, 1960) and rats (Rockich and Blouin, 1999;Ahn et al, 2003;Chung et al, 2003;Moon et al, 2003;Baek et al, 2006). The use of 6-OHCZX as a chemical probe has been reported to assess the activity of CYP2E1 in vitro and in vivo, due to the good correlation between the formation rate of 6-OHCZX and the CYP2E1 activity in humans (Coney and Burns, 1960) and rats (Rockich and Blouin, 1999).…”

Section: Chlorzoxazone (Czx)mentioning

confidence: 99%

Effects of endotoxin derived from Escherichia coli lipopolysaccharide on the pharmacokinetics of drugs

Yang

2008

Arch. Pharm. Res.

Self Cite

Lipopolysaccharide (LPS) endotoxin is an active component in the outer membrane of Gram-negative bacteria. LPS is usually used as an animal model of chronic inflammation such as sepsis. During inflammation, development of diarrhea, and changes in the plasma protein bindings, in the hepatic and/or intestinal microsomal cytochrome P450 (CYP) isozymes, and in the renal excretion of drugs have been reported. Thus, in rats pretreated with lipopolysaccharide endotoxin isolated from Escherichia Coli (ECLPS rats), the absorption, the distribution, the metabolism, and the excretion of drugs could be expected to alter. Interestingly, in ECLPS rats, the time-dependent effects on the hepatic CYP isozymes have been reported. Thus, in ECLPS rats, the pharmacokinetics of drugs which are mainly metabolized via hepatic CYP isozymes could be expected to be time-dependent. In this review, an attempt to explain changes in the pharmacokinetics of drugs reported in the literature was made in terms of hepatic CYP isozyme changes or urinary excretion changes in ECLPS rats.

“…CZX, once used as a skeletal muscle relaxant for the treatment of painful muscle spasms (Chen and Yang, 1996), primarily undergoes hydroxylation to form 6-hydroxychlorzoxazone (6-OHCZX), which is primarily catalyzed via CYP2E1 in humans (Conney and Burns, 1960) and rats (Rockich and Blouin, 1999;Kim et al, 2002b;Ahn et al, 2003;Chung et al, 2003;Moon et al, 2003;Baek et al, 2006). 6-OHCZX can be used as a chemical probe to assess the activity of the CYP2E1 in vitro and in vivo, due to the good correlation between the formation rate of 6-OHCZX and CYP2E1 activity in humans (Conney and Burns, 1960) and rats (Rockich and Blouin, 1999).…”

Section: Chlorzoxazone (Czx)mentioning

confidence: 99%

Effects of water deprivation on drug pharmacokinetics: Correlation between drug metabolism and hepatic CYP isozymes

2008

Arch. Pharm. Res.

Self Cite

Male Sprague-Dawley rats deprived of water for 72 h (a rat model of dehydration) showed no change in protein expression of the hepatic microsomal cytochrome P450 (CYP) 1A2, 2B1/2, 2C11, or 3A1/2, but an increase in protein expression (3-fold) and mRNA level (2.6-fold) of CYP2E1. Glucose feeding instead of food normalized CYP2E1 protein expression during dehydration. Here, we review how dehydration can change the pharmacokinetics of drugs reported in the literature via changing CYP isozyme levels. We also discuss how dehydration changes the pharmacokinetics of drugs that are metabolized via renal DHP-I, or are mainly excreted in the urine and bile, and form conjugates.