Disease relevance of NSC 24955

• The 6-hydroxychlorzoxazone area under the plasma concentration-time curve was inversely related to CL(cr), even within the range of normal renal function, resulting in chlorzoxazone metabolic ratio values that were substantially higher in subjects with kidney disease [1].
• Estimation of the fractional clearance of 6-hydroxychlorzoxazone showed that obesity increased this parameter to a similar extent as oral clearance [2].

High impact information on NSC 24955

• RESULTS: A linear model with first-order absorption for chlorzoxazone and first-order formation for 6-hydroxychlorzoxazone simultaneously described the disposition of both compounds [1].
• Impaired 6-hydroxychlorzoxazone elimination in patients with kidney disease: Implication for cytochrome P450 2E1 pharmacogenetic studies [1].
• Chlorzoxazone was found to be oxidized only to 6-hydroxychlorzoxazone in human liver microsomes [3].
• Chlorzoxazone (CZX) primarily undergoes hydroxylation, catalyzed mainly by CYP2E1, to form 6-hydroxychlorzoxazone (OH-CZX) rats [4].
• 6-Hydroxychlorzoxazone formation rate was unaffected by TBI in brain cortical microsomes [5].

Biological context of NSC 24955

• CYP2E1 activity was expressed as a hydroxylation index (HI = mmole oral chlorzoxazone dose/mmole 6-hydroxychlorzoxazone in 8-hour urine) [6].
• Dose dependency in chlorzoxazone metabolism was shown by a 30% increase (P < 0.05) in the dose-normalized area under the concentration-time curve (AUC) of chlorzoxazone and lower incremental dose-normalized urinary recovery of 6-hydroxychlorzoxazone at early timepoints after the 750-mg dose [7].
• In this study, comparative pharmacokinetics of CZX and 6-hydroxychlorzoxazone (OH-CZX) were conducted in rats pretreated with an inhibitor or inducer of P450 2E1 [8].

Anatomical context of NSC 24955

• Chlorzoxazone, a prescribed skeletal muscle relaxant, is metabolized to 6-hydroxychlorzoxazone by CYP2E1 and has been advocated as a specific probe of this enzyme on the basis of microsomal studies [9].

Associations of NSC 24955 with other chemical compounds

• Study of the fragmentation mechanism of protonated 6-hydroxychlorzoxazone: application in simultaneous analysis of CYP2E1 activity with major human cytochrome P450s [10].
• The CYP2E1 inhibitor, 4-methylpyrazole, inhibited the formation of 6-hydroxychlorzoxazone in brain, kidney, and liver microsomes [5].

Gene context of NSC 24955

• Cells from a single 35-mm plate catalyzed the formation of 1.02 nmol 6-hydroxychlorzoxazone/10(6) cells/h or about 127 pmol/mg total cell protein/min [11].
• The DI-GCE/MS/MS method demonstrates acceptable accuracy and precision for the simultaneous quantification of 1'-hydroxymidazolam, dextrorphan and 6-hydroxychlorzoxazone in microsomal incubations [12].
• Effects of cytochrome P450 2E1 modulators on the pharmacokinetics of chlorzoxazone and 6-hydroxychlorzoxazone in rats [8].
• A sensitive and reproducible method is described for the determination of the cytochrome P450 enzyme 2E1 substrate chlorzoxazone and its primary metabolite 6-hydroxychlorzoxazone in human plasma and urine [13].

Analytical, diagnostic and therapeutic context of NSC 24955

• Chlorzoxazone and 6-hydroxychlorzoxazone concentrations were determined by HPLC [14].
• Chlorzoxazone and 6-hydroxychlorzoxazone in serum and urine were analysed by high-performance liquid chromatography [15].

References