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• W2134857210 startingPage "1914" @default.
• W2134857210 abstract "Naturally occurring furanocoumarin compounds psoralen (PRN) and isopsoralen (IPRN) are bioactive constituents found in herbaceous plants. They are widely used as active ingredients in several Chinese herbal medicines. In this study, the CYP1A2 inhibitory potential of PRN and IPRN was investigated in rats in vitro and in vivo as well as in human liver microsomes. Both compounds exhibited reversible and time-dependent inhibition toward rat microsomal cyp1a2. The IC₅₀, <i>k</i>_inact, and <i>K</i>_I values were 10.4 ± 1.4 <i>μ</i>M, 0.060 ± 0.002 min⁻¹, and 1.13 ± 0.12 <i>μ</i>M for PRN, and 7.1 ± 0.6 <i>μ</i>M, 0.10 ± 0.01 min⁻¹, and 1.95 ± 0.31 <i>μ</i>M for IPRN, respectively. In human liver microsomal incubations, potent reversible CYP1A2 inhibition was observed for both compounds, with IC₅₀ values of 0.26 ± 0.01 <i>μ</i>M and 0.22 ± 0.03 <i>μ</i>M for PRN and IPRN, respectively. However, time-dependent inhibition was only observed for IPRN, with <i>k</i>_inact and <i>K</i>_I values of 0.050 ± 0.002 min⁻¹ and 0.40 ± 0.06 <i>μ</i>M, respectively. Coadministration with PRN or IPRN significantly inhibited cyp1a2 activity in rats, with the area under the curve (AUC) of phenacetin increasing more than 5-fold. Simcyp simulation predicted that PRN would cause 1.71- and 2.12-fold increases in the phenacetin AUC in healthy volunteers and smokers, respectively. IPRN, on the other hand, would result in 3.24- and 5.01-fold increases in phenacetin AUCs in healthy volunteers and smokers, respectively. These findings represent the first detailed report comparing the potential drug–drug interactions of PRN and IPRN, and provide useful information for balancing safe and efficacious doses of PRN and IPRN." @default.
• W2134857210 created "2016-06-24" @default.
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• W2134857210 date "2013-08-23" @default.
• W2134857210 modified "2023-10-01" @default.
• W2134857210 title "Identification and Characterization of Psoralen and Isopsoralen as Potent CYP1A2 Reversible and Time-Dependent Inhibitors in Human and Rat Preclinical Studies" @default.
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• W2134857210 doi "https://doi.org/10.1124/dmd.113.053199" @default.
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