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Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...

Phase II Reactions: Glucuronidation

Phase II Reactions: Glucuronidation

Glucuronidation, a pivotal phase II biotransformation process, involves the coupling of glucuronic acid to a drug or xenobiotic. Given its widespread occurrence and critical role in drug metabolism, it's considered the most crucial phase II reaction. It enhances the water solubility of substances, aiding their expulsion from the body. The driving force behind these reactions is a group of enzymes known as UDP-glucuronosyltransferases (UGTs). UGTs facilitate the transfer of a glucuronic acid...

Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids

Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids

Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2 (COX-2),...

Drug Metabolism: Phase II Reactions

Drug Metabolism: Phase II Reactions

Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...

Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents

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Related Experiment Video

Updated: Jun 18, 2026

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells

Published on: October 10, 2025

Glucarpidase following high-dose methotrexate: update on development.

Daniel M Patterson¹, Siow Ming Lee

¹UCL Cancer Institute and University College Hospital, Department of Oncology, London, UK.

Expert Opinion on Biological Therapy

|November 21, 2009

Summary

Glucarpidase rapidly reduces toxic methotrexate levels, preventing kidney damage. This enzyme is effective in emergencies but awaits marketing approval in the EU and USA.

Related Experiment Videos

Last Updated: Jun 18, 2026

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells

Published on: October 10, 2025

Area of Science:

Biochemistry
Pharmacology
Enzymology

Background:

Glucarpidase, a recombinant carboxypeptidase G2 enzyme, metabolizes methotrexate (MTX).
High-dose MTX can cause severe toxicities, including renal failure.
Carboxypeptidase enzymes are naturally occurring and play vital roles in biological processes.

Purpose of the Study:

To review the discovery and pre-clinical data of glucarpidase.
To summarize compassionate use studies of glucarpidase in MTX toxicity.
To discuss the current developmental status and potential of glucarpidase.

Main Methods:

Review of pre-clinical data on glucarpidase efficacy.
Analysis of compassionate use studies in patients with MTX-induced nephrotoxicity.
Assessment of clinical trial data regarding glucarpidase administration.

Main Results:

Glucarpidase effectively and rapidly reduces MTX levels.
Compassionate use cases demonstrate glucarpidase's utility in managing MTX toxicity and renal failure.
Pre-clinical studies confirm glucarpidase's high efficacy in MTX level reduction.

Conclusions:

Glucarpidase is a valuable therapeutic option for emergency situations involving high-dose MTX.
Further data from Phase I/II studies are needed for routine prophylactic use.
Marketing approval in the EU and USA is pending further clinical evaluation.