Glucuronic acid, conjugation

Hepatic metabolism No Yes oxidation and hydroxylation induces liver enzymes to increase its metabolism and other drugs Yes oxidation and conjugation Yes oxidation and glucuronide conjugation Yes glucuronic acid conjugation Induces its own metabolism in normal volunteers... 

P2. Pollack, R. L., and Eades, C. H., Glucuronic acid conjugates of aspartic and glutamic acids in urine. Science 119, 510-511 (1954). 

Although UGTs catalyze only glucuronic acid conjugation, CYPs catalyze a variety of oxidative reactions. Oxidative biotransformations include aromatic and side chain hydroxylation, N-, O-, S-dealkylation, N-oxidation, sulfoxidation, N-hydroxylation, deamination, dehalogenation and desulfation. The majority of these reactions require the formation of radical species this is usually the rate-determining step for the reactivity process [28]. Hence, reactivity contributions are computed for CYPs, but a different computation is performed with the UGT enzyme (as described in Section 12.4.2). 

The dynamics of TFM and its glucuronic acid conjugate in rainbow trout were reported by Hunn and Allen (17). The major increase in the accumulation of TFM conjugate in the bile occurred at the same time (between 0.75 and 1.0 h of exposure) that the concentration of conjugate in the plasma dropped. 

C2. Childs, B., Sudbury, J. B., and Migeon, C. J., Glucuronic acid conjugation by patients with familial nonhemolytic jaundice and their relatives. Pediatrics 23, 903-913 (1959). 

Lamotrigine Partial (adults) 55 Glucuronic acid conjugation to inactive metabolites 94% excreted in urine, 2% in feces... 

Metabolism/Excretion-The apparent elimination half-life is 10.8 hours (range, 9.1 to 14.4 hours). Of a 4 mg oral dose, 25% is excreted unchanged in the feces, and 1.3% is excreted in the urine as free drug and glucuronic acid conjugate within 3 days. 

Pharmacokinetics Rapidly absorbed from the G1 tract. Protein binding 55%, Metabolized primarily by glucuronic acid conjugation. Excreted in the urine. Half-life 13-30 hr. 

Certain thiols may be conjugated directly through the sulfur atom (Fig. 4.55). Glucuronic acid conjugated directly to carbon atoms has been reported such as with the drug phenylbutazone. 

The mouse has less sulfotransferase activity with respect to the a-hydroxytamoxifen, but more glucuronosyl transferase activity. The resulting glucuronic acid conjugation is a clear detoxication pathway, as a stable metabolite is formed, which can be readily eliminated. Hence, the mouse is much less susceptible, and although some tamoxifen is covalently bound to liver DNA, no hepatic tumors have been detected. 

S-adrenoceptor an autonomic receptor, which is of two types, pi and p2. aglycone portion of molecule attached to glycoside as in a glucuronic acid conjugate. 

Absorption of pentachlorophenol is relatively rapid in all species studied, but elimination differs between species and also between sexes. Metabolism occurs through glucuronic acid conjugation and hydrolytic dechlorination to tetrachlorohydroquinone, which is further conjugated. In contrast to rodents, rhesus monkeys eliminate pentachlorophenol in urine unchanged (lARC, 1991). 

Xylenes are absorbed after inhalation and dermal exposure. Elimination after human exposure is rapid and mostly as urinary metabolites after oxidation to the methylbenzyl alcohols, methylbenzoic acids and their glycine and glucuronic acid conjugates. In mice inhaling /7 ra-xylene, methylhippurate accumulated in the nasal mucosa and olfactory bulb. 

A series of investigations of the metabolism of foreign organic compounds in the intact rabbit recently reported54-88 have given information about the kinetics of glucuronic acid conjugation in vivo. 

Some other benzodiazepines are metabolized by glucuronic acid conjugation. Of these, the clearance of temazepam was increased when oral contraceptives were administered concomitantly, but the clearance of loraze-pam and oxazepam was not (335). Again, it is unlikely that these are interactions of clinical importance. 

Salicylic acid clearance is higher in users of oral contraceptives, owing to increases in the glycine and glucuronic acid conjugation pathways. In eight men, eight women,... 

Table IV contains a listing of the substances whose administration has been reported as increasing the urinary glucuronic acid, and of compounds for which some evidence for glucuronic acid conjugation exists, but of which no glucuronic conjugate has actually been isolated. The compounds of Table III and, usually, their metabolic precursors have been omitted. Here, except as noted, specific references to the literature will be found in Williams text.1 Unfortunately, this list is not complete some of the references were found only by careful search, and there are probably many more buried in the literature.

---