Glucuro conjugates

Felgines, C., Strawberry anthocyanins are recovered in urine as glucuro- and sulfo-conjugates in humans, J. Nutr., 133, 1296, 2003. 

Cimetidine can impair benzodiazepine metabolism and lead to adverse effects (SEDA-18, 43). In contrast, a few benzodiazepines are metabolized exclusively by glucuro-nide conjugation (lorazepam, oxazepam, temazepam), and are therefore unaffected by concomitant therapy with cimetidine and other oxidation inhibitors (123). 

The lactam derivative dibenz[h/]l 4-oxazepin-ll-(lOH)-one is a primary metabolic product of metabolism and a direct precursor of the urinary hydroxylated metabolites. In rats, the lactam, a dihydro-CR metabolite, an amino alcohol of CR, and an arene oxide are metabolites in CR degradation. In the rat, the major mechanism for elimination is sulfate conjugation and biliary excretion to a limited extent. Phase I metabolism by microsomal mixed fimction oxidases involves reduction of CR to the amino alcohol, oxidation to form the lactam ring, and hydroxylation to form the hydroxylactams. Phase II conjugation reactions sulfate the hydroxylactam intermediates for renal elimination. Amino alcohol intermediates are conjugated with glucuro-nide for biliary secretion. 

Dichlorobenzene is well absorbed orally and by inhalation. The highest concentrations are found in the adipose tissue. It is rapidly oxidized to phenolic compounds and metabolized to sulfate and glucuro-ate conjugates. The major metabolite is 2,5-dichloro-phenol. From 91% to 97% is excreted in the urine within 5 days. 

Fig. 31.29 Different metabolic pathways of p-amino-salicylic acid. Several conjugating enzymes are involved glycine TV-acyltransferases (reaction 1), UDP-glucuro-nosyltransferases (acyl-, ether-, A/-glucuronides, reactions 2, 4 and 6, respectively), sulfotransferases (reactions 3 and 5), A/-acetyltransferases (reaction 7).

The triazolo-and related benzodiazepines, such as alprazolam, midazolam and triazolam, are mainly metabolised by hydroxylation, mediated by CYP3A4, to active compounds, which then rapidly undergo glucuro-nide conjugation. 

Testosterone circulating in the blood is mainly metabolized in the liver to androstenedione which is converted via intermediates into androsterone and its 3 isomer. These are then excreted in urine as glucuro-nides or sulfate conjugates. 

Figure 9.12), In human blood and urine samples, only thymol and its conjugates, thymol glucuro-nide and sulfate, could be identi ed (Meesters et ah, 2009). 

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