NotesMetabolic Deesterification of Tazarotene in Human Blood and Rat and HumanLiver Microsomes
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Cited by (28)
Drug and pro-drug substrates and pseudo-substrates of human butyrylcholinesterase
2023, Biochemical PharmacologyApplication of PBPK modeling in predicting maternal and fetal pharmacokinetics of levetiracetam during pregnancy
2023, European Journal of Pharmaceutical SciencesCitation Excerpt :The method used here was designed to estimate the activity of Type B esterase enzymes in pregnant women via cholinesterase activity in RBCs, because the Type B esterase enzymes involved in the reaction were similar to isoenzymes of cholinesterase. Based on previous data (Strolin Benedetti et al., 2003; Madhu et al., 1997; Patsalos et al., 2006; de Peyster et al., 1994), assuming constant clearance of Type B esterase enzymes in the first and second trimesters, the third-trimester fold was estimated to be 1.2. Further details were provided in the Supplemental section S1.2.
Insights into the degradation chemistry of tazarotene, a third generation acetylenic retinoid: LC-HRMS (Orbitrap), LC-MS<sup>n</sup> and NMR characterization of its degradation products, and prediction of their physicochemical and ADMET properties
2020, Journal of Pharmaceutical and Biomedical AnalysisCitation Excerpt :Chemically, it is ethyl 6-[(4,4dimethylthiochroman-6-yl)ethynyl]nicotinate [4]. The drug is a monoethyl ester prodrug, which gets hydrolysed by esterases to its active metabolite, tazarotenic acid (6-((4,4-dimethylthiochroman-6-yl)ethynyl)nicotinic acid) [5,6]. Both TZR and its active metabolite (tazarotenic acid) undergo further metabolism via oxidation to corresponding sulfoxides and sulfones [5,7–9].
Simultaneous determination of tazarotene and its active metabolite tazarotenic acid in minipig plasma by LC-MS/MS and its application in pharmacokinetic study after topical administration of tazarotene gel
2015, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life SciencesCitation Excerpt :In the therapy of acne vulgaris, tazarotene has shown the property to modulate the pathogenic factors of acne and decrease the proliferation of Propionibacterium acnes [4]. After topical administration, tazarotene undergoes esterase hydrolysis to form its active metabolite tazarotenic acid in skin and plasma, and both analytes are present at low concentration level of pg/mL in human plasma [3,5–7]. The main adverse effects after administration of tazarotene are cutaneous symptoms, asthenia, serum lipid elevation, and hair loss due to high systemic exposure of tazarotene and tazarotenic acid [8].
Disposition and biotransformation of the acetylenic retinoid tazarotene in humans
2005, Journal of Pharmaceutical SciencesCitation Excerpt :This finding is consistent with a previous pharmacokinetic study that demonstrated the main circulating agent to be tazarotenic acid, with Tmax ranging 2 to 3 h postdose, following tazarotene oral administration.10 The rapid blood hydrolysis of tazarotene is mediated by one or more paraoxon-inhibitable esterases.11 A proportion of tazarotenic acid, accounting for 19.2 ± 3.2% of the dose, was then further metabolized to tazarotenic acid sulfoxide, an inactive metabolite, that was mainly excreted in the urine.
Intramolecular disulfide bonds are required for folding hydrolase B into a catalytically active conformation but not for maintaining it during catalysis
2004, Biochemical and Biophysical Research Communications