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- W2355852019 abstract "Objective: To evaluate the effect of the anti-HIV traditional Chinese medicine prescription ZYSH on CYP3A4 activity of human liver microsomes,indinavir metabolic enhancement in vitro,and the increased exposure content of indinavir in SD rats.Methods: The ZYSH extract was diluted in PBS and pre-incubated with human liver microsomes for 15 min,and incubated with testosterone and β-NADPH for 30 min.The enzyme activities and formation of 6β-OH testosterone were quantified by LC-MS/MS.Inhibition potentials(IC50) were calculated.The extract(5 and 10 mg·mL-1) was pre-incubated with pooled human liver microsomes for 15 min,and further incubated with indinavir and β-NADPH for 0,5,15,30,60,and 120 min.Half-life(t1/2) of indinavir parent was calculated and effects of ZYSH on metabolism of indinavir were evaluated in SD rats.Rats were intragastrically administered with ZYSH for 7 days,and then indinavir was given.Plasma concentration of indinavir was quantified to calculate the plasma exposure.Results: ZYSH obviously inhibited the CYP3A4 activity and the IC50 value was 3.21 mg·mL-1;therefore it also inhibited the metabolism of indinavir in vitro.The t1/2 of indinavir was prolonged from 47.5 min to 184 and 1 404 min after incubated with ZYSH at concentrations of 5 and 10 mg·mL-1;while the intrinsic clearance reduced from 36.6 mL·min-1·kg-1 to 9.4 and 1.2 mL·min-1·kg-1,respectively.The AUC of indinavir in SD rats treated with ZYSH for 7 days were 2.1 folds of the control rtas treated with saline.Conclusion: ZYSH can slow down metabolism of indinavir through inhibiting the enzyme activity of CYP3A4 in human liver microsomal in vitro and may increase plasma exposure in SD rats through metabolic enhancement." @default.
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- W2355852019 date "2012-01-01" @default.
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- W2355852019 title "Enhanced anti-HIV efficacy of indinavir by metabolic interactions with the traditional Chinese medicine prescription ZYSH" @default.
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