Carboxylesterase in the liver and small intestine of experimental animals and human

Taketani, Megumi; Shii, Mayumi; Ohura, Kayoko; Ninomiya, Shinichi; Imai, Teruko

doi:10.1016/j.lfs.2007.07.026

Cited by 184 publications

(174 citation statements)

References 23 publications

Supporting

Mentioning

155

Contrasting

Unclassified

Order By: Relevance

“…Thus, outcomes from PK assessment could not be completely extrapolated to humans as long as interspecies differences existed in the enzymes related to FF metabolism. According to a previous report, no significant differences were reported between human and rat hepatic CES1A1 activity; furthermore, plasma PK behavior of FA in humans was in agreement with PK data in rats obtained in our study (Lovin et al, 2003;Taketani et al, 2007). Thus, FA might also exhibit high dermal exposure in humans as observed in rats.…”

Section: Discussionsupporting

confidence: 91%

New Photosafety Assessment Strategy Based on the Photochemical and Pharmacokinetic Properties of Both Parent Chemicals and Metabolites

et al. 2015

View full text Add to dashboard Cite

Photoreactivity and dermal/ocular deposition of compounds have been recognized as key considerations for evaluating the phototoxic risk of compounds. Because some drugs are known to cause phototoxic reactions via generation of potent phototoxic metabolites, photosafety assessments on parent drugs alone may lead to false predictions about their photosafety. This study aimed to establish a new photosafety assessment strategy for evaluating the in vivo phototoxic potential of both a parent substance and its metabolites. The in vivo phototoxic risk of fenofibrate (FF) and its metabolites, fenofibric acid (FA) and reduced fenofibric acid, were evaluated based on photochemical and pharmacokinetic analyses. FF and FA exhibited intensive UV absorption, with molar extinction coefficient values of 17,000 (290 nm) and 14,000 M 21 cm 21 (295 nm), respectively. Superoxide generation from FA was significantly higher than from FF, and a marked increase in superoxide generation from FF was observed after incubation with rat hepatic S9 fractions, suggesting enhanced photoreactivity of FF after metabolism. FA showed high dermal/ocular deposition after oral administration (5 mg/kg, p.o.) although the concentration of FF was negligible, suggesting high exposure risk from FA. On the basis of these findings, FA was deduced to be a major contributor to phototoxicity induced by FF taken orally, and this prediction was in accordance with the results from in vitro/in vivo phototoxicity tests. Results from this study suggest that this new screening strategy for parent substances and their metabolites provides reliable photosafety information on drug candidates and would be useful for drug development with wide safety margins.

show abstract

Section: Discussionsupporting

confidence: 91%

New Photosafety Assessment Strategy Based on the Photochemical and Pharmacokinetic Properties of Both Parent Chemicals and Metabolites

et al. 2015

View full text Add to dashboard Cite

show abstract

“…It includes human intestinal CE (CES2A1), 34,[40][41][42][43][44] rat CES2 (CES2A10), 22) rat intestinal CE RL4 (rCES2) (CES2A6), 45) rabbit form 2 46) and hamster AT51 (CES2A11). 47) CES3 includes ES-male (CES3A2) and human CES3 (CES3A1).…”

Section: Novel Classification and Nomenclature Of Mammalian Cesunclassified

Carboxylesterases: structure, function and polymorphism in mammals

Satoh

Hosokawa

2010

J. Pestic. Sci.

View full text Add to dashboard Cite

“…It includes human intestinal CarbE (CES2A1) (Schwer et al, 1997;Humerickhouse et al, 2000;Imai et al, 2006;Taketani et al, 2007;Yang et al, 2007;Shi et al, 2008), rCES2 (CES2A10) (Furihata et al, 2005), rat intestinal CarbE RL4 (rCES2) (CES2A6) (Furihata et al, 2003), rabbit form 2 (Ozols, 1989) and hamster AT51 (CES2A11) (Sone et al, 1994). CES3 includes ES-male (CES3A2) and human CES3 (CES3A1) (Aida et al, 1993;Sanghani et al, 2004).…”

Section: Introductionunclassified

Carboxylesterases: Structure, Function and Polymorphism

Satoh¹,

Hosokawa²

2009

Biomolecules and Therapeutics

View full text Add to dashboard Cite

-This review covers current developments in molecular-based studies of the structure and function of carboxylesterases. To allay the confusion of the classic classification of carboxylesterase isozymes, we have proposed a novel nomenclature and classification of mammalian carboxylesterases on the basis of molecular properties. In addition, mechanisms of regulation of gene expression of carboxylesterases by xenobiotics, and involvement of carboxylesterase in drug metabolism are also described.

show abstract

Carboxylesterase in the liver and small intestine of experimental animals and human

Cited by 184 publications

References 23 publications

New Photosafety Assessment Strategy Based on the Photochemical and Pharmacokinetic Properties of Both Parent Chemicals and Metabolites

New Photosafety Assessment Strategy Based on the Photochemical and Pharmacokinetic Properties of Both Parent Chemicals and Metabolites

Carboxylesterases: structure, function and polymorphism in mammals

Carboxylesterases: Structure, Function and Polymorphism

Contact Info

Product

Resources

About