Preclinical pharmacokinetics and metabolism of 6-(4-(2,5-difluorophenyl)oxazol-5-yl)-3-isopropyl-[1,2,4]-triazolo[4,3-a]pyridine, a novel and selective p38α inhibitor: identification of an active metabolite in preclinical species and human liver microsomes

2006 ◽  
Vol 27 (8) ◽  
pp. 371-386 ◽  
Author(s):  
Amit S. Kalgutkar ◽  
Heather L. Hatch ◽  
Frederick Kosea ◽  
Hang T. Nguyen ◽  
Edna F. Choo ◽  
...  
Keyword(s):  
Active Metabolite ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Preclinical Pharmacokinetics ◽  
Preclinical Species

Selective Inhibition of Cytochrome P450 2D6 by Sarpogrelate and Its Active Metabolite, M-1, in Human Liver Microsomes

2013 ◽  
Vol 42 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Doo-Yeoun Cho ◽  
Soo Hyeon Bae ◽  
Joeng Kee Lee ◽  
Yang Weon Kim ◽  
Bom-Taeck Kim ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Active Metabolite ◽  
Human Liver ◽  
Liver Microsomes ◽  
Selective Inhibition ◽  
Human Liver Microsomes ◽  
Cytochrome P450 2D6 ◽  
P450 2D6

In vitro hepatic conversion of the anticancer agent nemorubicin to its active metabolite PNU-159682 in mice, rats and dogs: A comparison with human liver microsomes

2008 ◽  
Vol 76 (6) ◽  
pp. 784-795 ◽  
Author(s):  
Luigi Quintieri ◽  
Marianna Fantin ◽  
Pietro Palatini ◽  
Sara De Martin ◽  
Antonio Rosato ◽  
...  
Keyword(s):  
Active Metabolite ◽  
Human Liver ◽  
Anticancer Agent ◽  
Liver Microsomes ◽  
Human Liver Microsomes

Thein vitro metabolism of desglymidodrine, an active metabolite of prodrug midodrine by human liver microsomes

2004 ◽  
Vol 29 (3) ◽  
pp. 179-186 ◽  
Author(s):  
Masayuki Akimoto ◽  
Izumi Iida ◽  
Hiroki Itoga ◽  
Atsunori Miyata ◽  
Shizuko Kawahara ◽  
...  
Keyword(s):  
Active Metabolite ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes

Microsomal metabolism of carbamazepine and oxcarbazepine in liver and placenta

1998 ◽  
Vol 17 (12) ◽  
pp. 668-676 ◽  
Author(s):  
P Myllynen ◽  
P Pienimäki ◽  
H Raunio ◽  
K Vähäkangas
Keyword(s):  
Active Metabolite ◽  
Human Liver ◽  
Mouse Liver ◽  
Covalent Binding ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Unknown Metabolite ◽  
Order Of Magnitude ◽  
Unidentified Metabolite

Metabolism of both carbamazepine (CBZ) and oxcarbaze-pine (OCBZ) were catalyzed by human liver microsomes and microsomes from livers of CBZ-induced or non-induced C57BL/6 mice. Human placental microsomes metabolized only OCBZ. Mouse liver microsomes metabolized CBZ to carbamazepine-10,11-epoxide (CBZ-E), 10- hydroxy-10,11-dihydro-carbamazepine (10-OH-CBZ), 3- hydroxy-carbamazepine (3-OH-CBZ), 10,11-trans-dihydroxy-10,11-dihydro-carbamazepine (10,11-D) and to an unidentified metabolite. CBZ-pretreatment of mice increased both ethoxyresorufin O-deethylase activity in the liver and the amount of CBZ-E in microsomal incubations regardless of the age of mice. Human liver microsomes catalyzed the formation of CBZ to 9-hydroxymethyl-10-carbamoyl acridan (9-AC) in addition to CBZ-E, 3-OH-CBZ and 10-OH-CBZ. OCBZ was metabolized to its active metabolite in all incubations. An unknown metabolite was also present in some of the incubations. Human liver microsomes catalyzed only minute covalent binding of CBZ and OCBZ to DNA. Binding of OCBZ was, however, one order of magnitude greater than binding of CBZ. Human placental micro-somes from the mothers on CBZ therapy did not catalyze CBZ metabolism. The same microsomes catalyzed OCBZ metabolism to 10-OH-CBZ and to an unknown metabolite. These results indicate autoinduction in CBZ metabolism in mouse liver. Due to the higher binding of OCBZ than CBZ to DNA in vitro, further studies on the potential mutagenicity of OCBZ may be warranted.

Sign in / Sign up

Export Citation Format

Share Document