Characterization of benzazepine UDP-glucuronosyl-transferases in laboratory animals and man.

  title={Characterization of benzazepine UDP-glucuronosyl-transferases in laboratory animals and man.},
  author={Kristian Tage Hansen and Katinka Stentoft},
  journal={Xenobiotica; the fate of foreign compounds in biological systems},
  volume={25 6},
  • K. HansenK. Stentoft
  • Published 1995
  • Biology, Chemistry
  • Xenobiotica; the fate of foreign compounds in biological systems
1. The O-glucuronidation of two dopamine D1 receptor antagonists, Odapipam and Berupipam, were studied in hepatic microsomal fractions from mouse, rat, rabbit, dog, pig, and man using 14C-UDP-glucuronic acid. 2. The influence of pH, detergent, gender, drug-metabolizing enzyme inducers, and age were examined. Detergents like the zwitterionic CHAPS and non-ionic Tween 20, Triton X-100, and Brij 35 stimulated the glucuronidation rate by up to 600% of native activity with the latter being most… 

Bis(hydroxyphenyl)methane—bisphenol F—metabolism by the HepG2 human hepatoma cell line and cryopreserved human hepatocytes

The metabolism of BPF in both HepG2 cells and human hepatocytes suggests the existence of a detoxification pathway, and these two cell models differ in metabolic capacity.

Normal-phase liquid chromatography-particle-beam mass spectrometry in drug metabolism studies of the dopamine receptor antagonist Odapipam and the muscarine M1 receptor agonist Xanomeline.

The results show that normal-phase hplc based on silica material is superior to reversed-phase-based systems in terms of selectivity and the use of non-aqueous solvents in combination with particle-beam mass spectrometry is advantageous.

Pharmacokinetics of new calcium channel antagonist clevidipine in the rat, rabbit, and dog and pharmacokinetic/pharmacodynamic relationship in anesthetized dogs.

Clevidipine is a high-clearance drug with a relatively small volume of distribution, resulting in an extremely short half-life in all species studied, and a significant gender difference in the clearance of the metabolite was observed in the rat.

Fentanyl-Induced Thrombocytopenia.

  • D. Rosas
  • Medicine, Biology
    American journal of therapeutics
  • 2020
The CHA2DS2-VASc score strongly correlates with glomerular filtration rate and predicts renal function decline over time in elderly patients with atrial fibrillation and chronic kidney disease and the Efficacy and safety of edoxaban in the ENGAGE AF-TIMI 48 trial.

Dabigatran Levels in Elderly Patients with Atrial Fibrillation: First Post-Marketing Experiences

It is demonstrated that elderly patients on reduced dabigatran exhibit significantly higher dabig atran levels than younger individuals on a reduced regimen, and similar levels compared with younger individuals with NV-AF and with younger patients on standard dabIGatran.

Anti-Xa Activity in Elderly Xabans-Treated Patients With Atrial Fibrillation.

A pilot, prospective, observational, postmarketing study in elderly patients with atrial fibrillation on xabans (rivaroxaban or apixaban) to assess the trough and peak AXaA in elderly rivaroxabanand apxaban-treated patients with AF found no significant differences.

Drug evaluation of clevidipine for acute hypertension

Clevidipine is an effective agent for reducing acute elevation in blood pressure in various settings, including hypertensive emergencies and perioperative hypertension with a good safety profile.



Characterization of a rat liver glucuronosyltransferase that glucuronidates the selective D1 antagonist, SCH 23390, and other benzazepines.

A rat liver glucuronosyltransferase with a unique substrate specificity toward selected dopaminergic agents is described.

Studies on the glucuronidation of dopamine D-1 receptor antagonists, SCH 39166 and SCH 23390, by human liver microsomes.

Results in hepatic microsomes from squirrel monkeys indicate that a unique human hepatic UGT may be involved in SCH 39166 glucuronidation, and substrates for morphine UDP-glucuronosyltransferase (UGT), and p-nitrophenol, an alternative substrate for numerous human hepatics UGTs, did not inhibit SCH 39165 glucuronidated.

Stable expression of a human liver UDP-glucuronosyltransferase (UGT2B15) with activity toward steroid and xenobiotic substrates.

Apparent KM and enzyme efficiency values for certain food-derived substrates for expressed UGT2B15 were similar to those determined for endobiotic substrates, suggesting that some naturally occurring substances are good substrate for this enzyme and that glucuronidation of endogenous compounds could be affected by xenobiotics derived from dietary sources.

SCH 39166, a novel dopamine D1 receptor antagonist: In vitro investigation of its glucuronidation and potential species differences

Results demonstrated that 3H‐SCH 39166 was glucuronidated by both rat and monkey liver microsomes, consistent with in vivo behavioral studies in squirrel monkeys, in which the duration of action of SCH 23390 was much shorter than SCH 39166.

Effect of different detergent systems on the molecular size of UDP glucuronosyltransferase and other microsomal drug-metabolizing enzymes.

The zwitterionic CHAPS is superior to other detergent systems for studies concerned with the purification of transferase enzymes, a microsomal system in which investigation of the number of different forms has been hampered by the instability of the enzyme upon solubilization and subsequent manipulation.

Isolation and purification of UDP-glucuronosyltransferases.

  • T. Tephly
  • Biology
    Chemical research in toxicology
  • 1990
Many of the UDPGTs have an extraordinarily broad substrate specificity; a few, however, are relatively specific for a given class of substrate (morphine, DT-1 UDP GTs).

Glucuronidation of the dopamine D-1 receptor antagonists NNC 0756 and NNC 0772 in liver microsomes.

High- and low-affinity reactions showed a high degree of stereoselectivity, primarily because of the large differences in Km values, suggesting the involvement of a single form of glucuronosyltransferase or possibly two forms, with similar affinity for NNC 0756.