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In vitro Inhibition of CYP3A4 by VitaePro

Syrstad, Ingvild Helø
Master thesis
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http://hdl.handle.net/11250/2418416
Issue date
2016
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  • Institutt for klinisk og molekylær medisin [1109]
Abstract
Introduction and aims: There has been an almost exponential growth within the nutritional supplement industry, and along with this, an increasing number of reported interactions between supplements and prescribed drugs have been observed. One of Scandinavia’s best-selling supplements, VitaePro, has been developed in four “generations” with varying constituents. The aim of this study was to investigate the in vitro inhibitory effect of the two latest products towards CYP3A4. Further, the inhibitory potency of the two products was compared. The two first generations have already been investigated in one earlier study of VitaePro and CYP3A4 Materials and methods: The experimental work was performed using human cDNA expressed CYP3A4, an NADPH regenerating system and with testosterone as substrate. After incubation with VitaePro, the formation of the metabolite 6-β-OH-testosterone was quantified using a validated high performance liquid chromatography (HPLC)-method. Based on the inhibition plots, inhibitory concentrations decreasing the enzyme activity by 50%, IC50-values, were calculated by non-linear regression. Ketoconazole (KTZ) was used as positive inhibitory control (PIC). Results and conclusion: VP3 inhibited CYP3A4 with IC50-values of 5.29±0.72 mg/mL and 3.77±0.83 mg/mL in the first and second experiment, respectively, and the corresponding values for VP4 were 0.14±0.03 mg/mL and 0.17±0.01 mg/L. Both generations proved to inhibit CYP3A4 in vitro, but VP4 to a greater extent than VP3. The 95% confidence intervals of the IC50-values showed a significant difference in inhibitory potency between VP3 and VP4, which presumably can be attributed to the Boswellia serrata extract added in VP4. Using theoretical approaches, one can hypothesize that VitaePro might be a candidate for in vivo effects, and this should be investigated in further trials.
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NTNU

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