Identification of sulfonyl-loxoprofen as novel phase 2 conjugate in rat

Riya Shrestha; Sanjita Paudel; Piljoung Cho; Aarajana Shrestha; Tae Cheon Jeong; Eung Seok Lee; Taeho Lee; Sangkyu Lee

doi:10.1002/bdd.2196

Identification of sulfonyl-loxoprofen as novel phase 2 conjugate in rat

Riya Shrestha, Sanjita Paudel, Piljoung Cho, Aarajana Shrestha, Tae Cheon Jeong, Eung Seok Lee, Taeho Lee, Sangkyu Lee

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Loxoprofen is a prodrug that exerts strong analgesic and anti-inflammatory effects through its active trans-alcohol metabolite, which is produced in the liver by carbonyl reductase. Previous metabolic studies have evaluated loxoprofen, but its sulfate and taurine conjugates have not yet been studied. We characterized the metabolomic profile of loxoprofen in rat plasma, urine, and feces using high-resolution mass spectrometry. We identified 17 metabolites of loxoprofen in the three different biological matrices, 13 of which were detected in plasma and feces and 16 in urine. Amongst these metabolites, two novel taurine conjugates (M12 and M13) and two novel acyl glucuronides (M14, M15) were identified for the first time in rats. In addition, we detected three novel sulfate conjugates (M9, M10, and M11) of loxoprofen. Further study of these metabolites of loxoprofen is essential in order to assess their potency and toxicity.

Original language	English
Pages (from-to)	234-241
Number of pages	8
Journal	Biopharmaceutics and Drug Disposition
Volume	40
Issue number	7
DOIs	https://doi.org/10.1002/bdd.2196
State	Published - Jul 2019
Externally published	Yes

Keywords

In vivo metabolism
Loxoprofen
rat
sulfonyl-loxoprofen conjugates

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@article{43f4d390896f4487969827d71408f2cd,

title = "Identification of sulfonyl-loxoprofen as novel phase 2 conjugate in rat",

abstract = "Loxoprofen is a prodrug that exerts strong analgesic and anti-inflammatory effects through its active trans-alcohol metabolite, which is produced in the liver by carbonyl reductase. Previous metabolic studies have evaluated loxoprofen, but its sulfate and taurine conjugates have not yet been studied. We characterized the metabolomic profile of loxoprofen in rat plasma, urine, and feces using high-resolution mass spectrometry. We identified 17 metabolites of loxoprofen in the three different biological matrices, 13 of which were detected in plasma and feces and 16 in urine. Amongst these metabolites, two novel taurine conjugates (M12 and M13) and two novel acyl glucuronides (M14, M15) were identified for the first time in rats. In addition, we detected three novel sulfate conjugates (M9, M10, and M11) of loxoprofen. Further study of these metabolites of loxoprofen is essential in order to assess their potency and toxicity.",

keywords = "In vivo metabolism, Loxoprofen, rat, sulfonyl-loxoprofen conjugates",

author = "Riya Shrestha and Sanjita Paudel and Piljoung Cho and Aarajana Shrestha and Jeong, \{Tae Cheon\} and Lee, \{Eung Seok\} and Taeho Lee and Sangkyu Lee",

note = "Publisher Copyright: {\textcopyright} 2019 John Wiley \& Sons, Ltd.",

year = "2019",

month = jul,

doi = "10.1002/bdd.2196",

language = "English",

volume = "40",

pages = "234--241",

journal = "Biopharmaceutics and Drug Disposition",

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TY - JOUR

T1 - Identification of sulfonyl-loxoprofen as novel phase 2 conjugate in rat

AU - Shrestha, Riya

AU - Paudel, Sanjita

AU - Cho, Piljoung

AU - Shrestha, Aarajana

AU - Jeong, Tae Cheon

AU - Lee, Eung Seok

AU - Lee, Taeho

AU - Lee, Sangkyu

PY - 2019/7

Y1 - 2019/7

N2 - Loxoprofen is a prodrug that exerts strong analgesic and anti-inflammatory effects through its active trans-alcohol metabolite, which is produced in the liver by carbonyl reductase. Previous metabolic studies have evaluated loxoprofen, but its sulfate and taurine conjugates have not yet been studied. We characterized the metabolomic profile of loxoprofen in rat plasma, urine, and feces using high-resolution mass spectrometry. We identified 17 metabolites of loxoprofen in the three different biological matrices, 13 of which were detected in plasma and feces and 16 in urine. Amongst these metabolites, two novel taurine conjugates (M12 and M13) and two novel acyl glucuronides (M14, M15) were identified for the first time in rats. In addition, we detected three novel sulfate conjugates (M9, M10, and M11) of loxoprofen. Further study of these metabolites of loxoprofen is essential in order to assess their potency and toxicity.

AB - Loxoprofen is a prodrug that exerts strong analgesic and anti-inflammatory effects through its active trans-alcohol metabolite, which is produced in the liver by carbonyl reductase. Previous metabolic studies have evaluated loxoprofen, but its sulfate and taurine conjugates have not yet been studied. We characterized the metabolomic profile of loxoprofen in rat plasma, urine, and feces using high-resolution mass spectrometry. We identified 17 metabolites of loxoprofen in the three different biological matrices, 13 of which were detected in plasma and feces and 16 in urine. Amongst these metabolites, two novel taurine conjugates (M12 and M13) and two novel acyl glucuronides (M14, M15) were identified for the first time in rats. In addition, we detected three novel sulfate conjugates (M9, M10, and M11) of loxoprofen. Further study of these metabolites of loxoprofen is essential in order to assess their potency and toxicity.

KW - In vivo metabolism

KW - Loxoprofen

KW - rat

KW - sulfonyl-loxoprofen conjugates

UR - https://www.scopus.com/pages/publications/85069504830

U2 - 10.1002/bdd.2196

DO - 10.1002/bdd.2196

M3 - Article

C2 - 31242324

AN - SCOPUS:85069504830

SN - 0142-2782

VL - 40

SP - 234

EP - 241

JO - Biopharmaceutics and Drug Disposition

JF - Biopharmaceutics and Drug Disposition

IS - 7

ER -

Identification of sulfonyl-loxoprofen as novel phase 2 conjugate in rat

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Keywords

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