Drug Glucuronidation in Clinical Psychopharmacology

@article{Liston2001DrugGI,
  title={Drug Glucuronidation in Clinical Psychopharmacology},
  author={Heidi L. Liston and John Seth Markowitz and C. Lindsay DeVane},
  journal={Journal of Clinical Psychopharmacology},
  year={2001},
  volume={21},
  pages={500-515}
}
Glucuronidation is a phase II metabolic process and one of the most common pathways in the formation of hydrophilic drug metabolites. At least 33 families of uridine diphosphate-glucuronosyltransferases have been identified in vitro, and specific nomenclature similar to that used to classify the cytochrome (CYP) P450 system has been established. The UGT1 and UGT2 subfamilies represent the most important of these enzymes in human drug metabolism. Factors affecting glucuronidation include the… Expand
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  • Medicine
  • The international journal of neuropsychopharmacology
  • 2003
TLDR
The importance of glucuronidation and the implications for psychiatry is illustrated as UGTs appear to be in small concentrations in brain tissue (and higher concentrations at brain capillaries). Expand
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Results are validated by comparison with the experimentally observed reaction rates and sites of metabolism, indicating that the presented models are suitable to provide the basis of a reactivity component within generalizable models to predict either FMO or UGT metabolism. Expand
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TLDR
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References

SHOWING 1-10 OF 138 REFERENCES
Drug glucuronidation in humans.
TLDR
Factors known to influence the pharmacokinetics of glucuronidated drugs in man, presumably via an effect on specific glucuronosyltransferases, include age, cigarette smoking, diet, certain disease states, coadministered drugs, ethnicity, genetics and hormonal effects. Expand
Glucuronidation of Drugs
TLDR
Examples of both direct and indirect contributions of glucuronides to net drug effects are described, indicating that morphine-6-glucuronide has analgesic activity and is a potent analgesic after administration to patients. Expand
UDP-glucuronosyltransferases and their role in metabolism and disposition of carcinogens.
  • K. Bock
  • Biology, Medicine
  • Advances in pharmacology
  • 1994
TLDR
Although glucuronidation usually leads to biologically inactive, watersoluble compounds, glucuronide formation may also generate metastable transport forms that can be hydrolyzed enzymatically or by acid, thereby determining the target of carcinogenicity. Expand
Glucuronidation: a dual control.
TLDR
The membrane environment of glucuronidation enzymes was shown to modulate their functional state as evaluated by the conjugating activity per enzymatic molecular unit, and it seems that this modulation can be attributed to different conformational states of the enzymes, depending on the physicochemical state of the membrane. Expand
Interindividual variability in the glucuronidation of (S) oxazepam contrasted with that of (R) oxazepam.
TLDR
The results suggest that the glucuronidation of the pharmacologically active (S) enantiomer of oxazepam is decreased in a significant percentage of Caucasian individuals. Expand
Characterization of Phase I and Phase II hepatic drug metabolism activities in a panel of human liver preparations.
  • K. Iyer, M. Sinz
  • Chemistry, Medicine
  • Chemico-biological interactions
  • 1999
TLDR
A human liver bank of 21 samples was characterized with respect to the activity of several important drug metabolizing enzymes and the fold variation of the Phase II enzymes was lower compared with the Phase I enzymes, with the exceptions of CYP1A2, CYP2E1, and FMO. Expand
Clinical Pharmacokinetics of Probenecid
TLDR
There are 2 primary clinical uses for probenecid: as a uricosuric agent in the treatment of chronic gout and as an adjunct to enhance blood levels of antibiotics (such as penicillins and Cephalosporins). Expand
Inhibition of acetaminophen and lorazepam glucuronidation in vitro by probenecid
TLDR
In vitro studies support in vivo results and confirm that the inhibition takes place at the hepatic level when probenecid was added. Expand
Glucuronidation of drugs by hepatic microsomes derived from healthy and cirrhotic human livers.
TLDR
In vitro metabolic data, which support the in vivo results, are likely to contribute to reasonably predict the level of impairment of hepatic clearance in patients with liver cirrhosis. Expand
(S)oxazepam glucuronidation is inhibited by ketoprofen and other substrates of UGT2B7.
TLDR
Inhibition studies suggest that the two diastereomeric glucuronidations are catalysed by different UGT isozymes, and there was competitive inhibition of (S)oxazepam glucuronidation by non-steroidal anti-inflammatory drugs (NSAIDs), including ketoprofen while (R)oxzepam glucoseuronidation was not equally inhibited by these compounds. Expand
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5
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