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1. ビリルビン過剰産生によるジルベール症候群および非抱合型ビリルビン過剰産生 gilberts syndrome and unconjugated hyperbilirubinemia due to bilirubin overproduction
2. ビリルビン代謝 bilirubin metabolism
3. クリグラー・ナジャー症候群 crigler najjar syndrome
4. 薬と肝臓：代謝および肝障害の機序 drugs and the liver metabolism and mechanisms of injury
5. 転移性大腸癌に対する全身化学療法：終了した臨床試験 systemic chemotherapy for metastatic colorectal cancer completed clinical trials

English Journal

Optimized methods for targeted Peptide-based quantification of human uridine 5'-diphosphate-glucuronosyltransferases in biological specimens using liquid chromatography-tandem mass spectrometry.

Sato Y1, Nagata M, Tetsuka K, Tamura K, Miyashita A, Kawamura A, Usui T.Author information 1Drug Metabolism Research Laboratories, Astellas Pharma Inc., Yodogawa-ku, Osaka, Japan (Y.S., M.N., A.M., A.K., T.U.); Astellas Research Institute of America LLC., Skokie, Illinois (K.Te., K.Ta.).AbstractThe aim of this study was to optimize methods for quantifying 13 uridine 5'-diphosphate-glucuronosyltransferase (UGT) isoforms (UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B10, 2B15, and 2B17) in human liver, intestinal, and kidney microsomes, and in recombinant human UGT-expressing insect cell membranes (rhUGTs) by targeted peptide-based quantification using liquid chromatography-tandem mass spectrometry. Production of targeted peptides was compared by combining three denaturing agents (urea, sodium deoxycholate, and octyl glucoside) and three denaturing temperatures (37°C, 60°C, and 95°C) followed by tryptic digestion for 2-20 hours. Denaturing conditions and digestion times yielding high production efficiency varied markedly among isoforms and specimens, indicating the importance of specific optimization. Each UGT isoform was quantified using the methods found to be optimal. The expression of 10 (1A1, 1A3, 1A4, 1A6, 1A9, 2B4, 2B7, 2B10, 2B15, and 2B17), 6 (1A1, 1A3, 1A4, 1A10, 2B7, and 2B17), and 3 (1A6, 1A9, and 2B7) isoforms was detected in human liver, intestinal, and kidney microsomes, respectively, and levels were reproducible using multiple protocols. All isoforms were quantified in rhUGTs. Determining the levels of UGTs in human tissue specimens and those in rhUGTs is important for estimating the contribution of glucuronidation to body clearance based on in vitro-in vivo extrapolation.
Drug metabolism and disposition: the biological fate of chemicals.Drug Metab Dispos.2014 May;42(5):885-9. doi: 10.1124/dmd.113.056291. Epub 2014 Mar 4.
The aim of this study was to optimize methods for quantifying 13 uridine 5'-diphosphate-glucuronosyltransferase (UGT) isoforms (UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B10, 2B15, and 2B17) in human liver, intestinal, and kidney microsomes, and in recombinant human UGT-expressing insec
PMID 24595681

In vitro metabolism of thyroxine by rat and human hepatocytes.

Richardson VM1, Ferguson SS, Sey YM, Devito MJ.Author information 1Pharmacokinetics Branch, Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency , Research Triangle Park, NC , USA .AbstractAbstract 1. The liver metabolizes thyroxine (T4) through two major pathways: deiodination and conjugation. Following exposure to xenobiotics, T4 conjugation increases through the induction of hepatic uridine diphosphate glucuronosyltransferase (UGT) in rodents; however, it is uncertain to what degree different species employ deiodination and conjugation in the metabolism of T4. The objective of this study was to compare the metabolism of T4 in untreated and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153)-treated primary sandwich-cultured hepatocytes from rat (SCRH) and human (SCHH). 2. Basal metabolite concentrations were 13 times higher in the medium of SCRH compared to SCHH. Metabolite distribution in the medium of SCRH versus SCHH was as follows: T4G, (91.6 versus 5.3%); T4S, (3.6 versus 4.4%) and T3 + rT3, (4.9 versus 90.3%). PCB 153 induced T4G in the medium of SCRH and SCHH; however, T4S and T3 + rT3 were changed but to a much lesser degree. 3. The results indicate that baseline T4 glucuronidation is greater in SCRH compared to SCHH. These data also suggest that glucuronidation may be a more important pathway for T4 metabolism in rats and deiodination may be a favored pathway in humans; however, with PCB 153 treatment these data support glucuronidation as a primary route of T4 metabolism in both rat and humans.
Xenobiotica; the fate of foreign compounds in biological systems.Xenobiotica.2014 May;44(5):391-403. doi: 10.3109/00498254.2013.847990. Epub 2013 Oct 31.
Abstract 1. The liver metabolizes thyroxine (T4) through two major pathways: deiodination and conjugation. Following exposure to xenobiotics, T4 conjugation increases through the induction of hepatic uridine diphosphate glucuronosyltransferase (UGT) in rodents; however, it is uncertain to what deg
PMID 24175917

The effect of UGT2B7*2 polymorphism on the pharmacokinetics of OROS® hydromorphone in Taiwanese subjects.

Vandenbossche J1, Richards H, Francke S, Bergh AV, Lu CC, Franc MA.Author information 1Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium.AbstractThis open-label, single-center, phase I study (NCT1487564) investigated the effect of uridine diphosphate-glucuronosyltransferase2B7 (UGT2B7 * 2) genetic polymorphism (H268Y) on the pharmacokinetics (PK) and safety of a single, oral, 16-mg dose of OROS® hydromorphone and its metabolite in healthy Taiwanese subjects. Plasma concentrations of hydromorphone and hydromorphone-3-glucuronide were determined in 28 subjects. PK parameters calculated included maximum plasma concentration (Cmax ); time to reach maximum plasma concentration (tmax ); area under plasma concentration-time curve from 0-48 hours (AUC0-48h ) and 0-infinite time (AUC∞ ); and hydromorphone-3-glucuronide:hydromorphone metabolic ratio (RM ). Mean plasma concentrations of hydromorphone and hydromorphone-3-glucuronide reached a maximum between 12-18 hours and 18-21 hours, respectively. No clear trend in PK parameters and no clinically significant differences in the incidence of treatment-emergent adverse events (TEAEs) were observed among different UGT2B7 genotypes. Our study found UGT2B7 polymorphism had no apparent effect on PK of OROS® hydromorphone; hydromorphone was well tolerated in pain-free volunteers when coadministered with naltrexone.
Journal of clinical pharmacology.J Clin Pharmacol.2014 Apr 7. doi: 10.1002/jcph.305. [Epub ahead of print]
This open-label, single-center, phase I study (NCT1487564) investigated the effect of uridine diphosphate-glucuronosyltransferase2B7 (UGT2B7 * 2) genetic polymorphism (H268Y) on the pharmacokinetics (PK) and safety of a single, oral, 16-mg dose of OROS® hydromorphone and its metabolite in healt
PMID 24706503

Japanese Journal

Inhibition of Morphine Glucuronidation in the Liver Microsomes of Rats and Humans by Monoterpenoid Alcohols

Ishii Yuji,Iida Naoko,Miyauchi Yuu [他]
Biological & pharmaceutical bulletin 35(10), 1811-1817, 2012-10
NAID 40019429250

Identification of Enzymes Responsible for the N-Oxidation of Darexaban Glucuronide, the Pharmacologically Active Metabolite of Darexaban, and the Glucuronidation of Darexaban N-Oxides in Human Liver Microsomes