Glucuronide, derivative

The steroids are highly lipophilic although they are found to be conjugated to hydrophilic ligands such as sulphates, glucuronide derivatives, or bound to plasma proteins (Nozaki, 2001). 

Excretion is primarily as glucuronide derivatives of the denitrated metabolite via kidney. IV infusion has rapid onset of action but effects are quickly reversed on stopping the infusion. So, it is used only in treatment of severe, recurrent angina at rest. 

Excretion, primarily in the form of glucuronide derivatives of the denitrated metabolites, is largely by way of the kidney. 

Pharmacokinetic properties Meptazinol has poor oral bioavailability due to extensive first-pass metabolism. Systemic availability is improved after rectal administration. Peak plasma concentrations are reached 30 min after rectal or intramuscular administration and plasma half-life is about 2 h. Plasma protein binding is low ( 30%). Meptazinole is extensively metabolized in the gut and liver mainly to the glucuronide derivative. Only about 10% is excreted unmetabolised in the faeces (Franklin, 1988). 

Delaforge M, Provost A, Perrin L, et al. Cytochrome P450-mediated oxidation of glucuronide derivatives example of estradiol-17P-glucuronide oxidation to 2-hydroxy-estradiol-17P-glucuronide by CYP 2C8. Drug Metab Dispos 2005 33 4664-73. 

Oxidation of glucose at C6 produces glucuronic acid. In the body, a common method for metabolizing drugs is to attach glucuronic acid. The resulting glucuronide derivative is water-soluble and easily excreted in the urine. 

Raradis, R. Rage, M. New active paclitaxel glucuronide derivative with improved water solubility. Int. J. Oncol., 1998, 12 391-394. 

The toxicity and bioavailability can be varied by conjugation to form new derivatives such as glu-curonides that are metabolized differently than the parent compound. An example is a glucuronide derivative of the aminophenol amide of dX -trans retinoic acid, fenretinamide (A-(4-hydroxyphenyl)-retinamide, 4-HPR) (117). 

In each form of cholestasis, atypical bile adds, such as monohydroxy bile acids, aUo-bile adds, 1- or 6-hydroxylated bile acids and their sulphated or glucuronidated derivatives, are found in the sermn and/or urine. In cholestasis, the increase in the neosynthesis of atypical bile adds that pass into the kidney can be seen as a compensatory mechanism which eliminates potentially hepatotoxic bile acids by renal clearance. The highest renal excretion quota is demonstrated by tetrahydroxy bile acids. 

Although this is a reversible reaction in vitro, the carboxylic acids formed are either converted rapidly to their ester glucuronide derivatives (a phase II reaction catalyzed by UDP-glucuronosyltransferase see below) or, if polar enough, are excreted unchanged. Consequently, the reverse reaction is generally not of significance in vivo. 

V. Glucuronide-derived Covalent Binding of Diflunisal to Bladder Tissue of Rats and Its Modulation by Urinary pH and Beta-glucuronidase," Biochem. Pharmacol. 46(7), 1175-1182 (1993). 

Stiehl, A., Becker, M., Czyan, P., Frohling, W., Kommerell, B.. Rottfaauwe, H. W., and Senn, M., Bile acids and their sulphated and glucuronidated derivatives in bile, plasma and urine of children with intrahepalic cholestasis Effects of phenobarbital treatment. Ear. J. CUn. Incest. 10, 307-316 (1980). 

A second flavone attractant for zoospores of A. cochlioides has also now been isolated from the leaves of spinach [65] and identified as 5,4 -dihydroxy-3,3 -dimethoxy-6,7-methylenedioxyflavone (71). Although this compound has already been found as a glucuronide derivative in spinach [66], the role of the aglycone 71 in the interaction between the host plant and its fungal pathogens has still to be determined. 

Kostiainen R, Tuominen J, Luukkanen L, Taskinen J, Green BN. Accurate mass measurements of some glucuronide derivatives by electrospray low resolution quadrupole mass spectrometry. Rapid Commun Mass Spectrom 1997 11 283-285. 

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