EMAIL THIS PAGE TO A FRIEND

Xenobiotica; the fate of foreign compounds in biological systems

Contribution of cytochrome P450 and UDT-glucuronosyltransferase to the metabolism of drugs containing carboxylic acid groups: risk assessment of acylglucuronides using human hepatocytes.


PMID 24575896

Abstract

1. In order to evaluate the inhibition activity of 1-aminobenzotriazole (ABT) and (-)-borneol (borneol) against cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT), the substrates of these metabolic enzymes were incubated with ABT and borneol in human hepatocytes. We found that 3 mM ABT and 300 μM borneol were the most suitable experimental levels to specifically inhibit CYP and UGT. 2. Montelukast, mefenamic acid, flufenamic acid, diclofenac, tienilic acid, gemfibrozil, ibufenac and repaglinide were markedly metabolized in human hepatocytes, and the metabolism of gemfibrozil, mefenamic acid and flufenamic acid was inhibited by borneol. With regard to repaglinide, montelukast, diclofenac and tienilic acid, metabolism was inhibited by ABT. Ibufenac was partly inhibited by both inhibitors. Zomepirac, tolmetin, ibuprofen, indomethacin and levofloxacin were moderately metabolized by human hepatocytes, and the metabolism of zomepirac, ibuprofen and indomethacin was equally inhibited by both ABT and borneol. The metabolism of tolmetin was strongly inhibited by ABT, and was also inhibited weakly by borneol. Residual drugs, telmisartan, valsartan, furosemide, naproxen and probenecid were scarcely metabolized. 3. Although we attempted to predict the toxicological risks of drugs containing carboxylic groups from the combination chemical stability and CLint via UGT, the results indicated that this combination was not sufficient and that clinical daily dose is important.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

PHR1057
Furosemide, Pharmaceutical Secondary Standard; Certified Reference Material
C12H11ClN2O5S
F0700000
Furosemide, European Pharmacopoeia (EP) Reference Standard
C12H11ClN2O5S
1287008
Furosemide, United States Pharmacopeia (USP) Reference Standard
C12H11ClN2O5S
Y0001493
Furosemide for peak identification, European Pharmacopoeia (EP) Reference Standard
C12H11ClN2O5S
G9518
Gemfibrozil
C15H22O3
91823
Gemfibrozil, analytical standard
C15H22O3
Y0000513
Gemfibrozil, European Pharmacopoeia (EP) Reference Standard
C15H22O3
PHR1286
Gemfibrozil, Pharmaceutical Secondary Standard; Certified Reference Material
C15H22O3
Y0000514
Gemfibrozil for system suitability, European Pharmacopoeia (EP) Reference Standard
C15H22O3
1356632
Ketoprofen, United States Pharmacopeia (USP) Reference Standard
C16H14O3
K2000000
Ketoprofen, European Pharmacopoeia (EP) Reference Standard
C16H14O3
34016
Ketoprofen, VETRANAL, analytical standard
C16H14O3
PHR1375
Ketoprofen, Pharmaceutical Secondary Standard; Certified Reference Material
C16H14O3
1362103
Levofloxacin, United States Pharmacopeia (USP) Reference Standard
C18H20FN3O4 · 0.5H2O
40922
Levofloxacin, analytical standard
C18H20FN3O4
M4267
Mefenamic acid
C15H15NO2
92574
Mefenamic acid, analytical standard
C15H15NO2
M0252600
Mefenamic acid, European Pharmacopoeia (EP) Reference Standard
C15H15NO2
N0630
Niflumic acid
C13H9F3N2O2
Y0000824
Niflumic acid, European Pharmacopoeia (EP) Reference Standard
C13H9F3N2O2
PHR1249
Phenacetin
C10H13NO2
PHR1094
Phenacetin melting point standard, Pharmaceutical Secondary Standard; Certified Reference Material
C10H13NO2
1514008
Phenacetin Melting Point Standard, United States Pharmacopeia (USP) Reference Standard
C10H13NO2
83580
Reserpine, crystallized, ≥99.0% (HPLC)
C33H40N2O9
R0200000
Reserpine, European Pharmacopoeia (EP) Reference Standard
C33H40N2O9
43530
Reserpine Standard for LC-MS, analytical standard, for LC-MS
C33H40N2O9
T8949
Telmisartan, ≥98% (HPLC), solid
C33H30N4O2
Y0000648
Telmisartan, European Pharmacopoeia (EP) Reference Standard
C33H30N4O2
1643419
Telmisartan, United States Pharmacopeia (USP) Reference Standard
C33H30N4O2
Y0000649
Telmisartan for peak identification, European Pharmacopoeia (EP) Reference Standard
C33H30N4O2