Avoiding PXR and CAR Activation and CYP3A4 Enzyme Induction

2013 ◽  
pp. 159-190 ◽  
Author(s):  
Michael W. Sinz
Keyword(s):  
Enzyme Induction ◽  
Cyp3a4 Enzyme

Effect of Rifampin on Apparent Clearance of Everolimus

2002 ◽  
Vol 36 (6) ◽  
pp. 981-985 ◽  
Author(s):  
John M Kovarik ◽  
Stefan Hartmann ◽  
Joaquim Figueiredo ◽  
Marisel Rouilly ◽  
Andreas Port ◽  
...  
Keyword(s):  
Enzyme Induction ◽  
Therapeutic Drug ◽  
Urine Excretion ◽  
Open Label ◽  
Average Decrease ◽  
Apparent Clearance ◽  
Full Study ◽  
Study Population ◽  
Cyp3a4 Enzyme ◽  
Single Sequence

OBJECTIVE: To assess the influence of the CYP3A4 enzyme inducer rifampin on the pharmacokinetics of the immunosuppressant everolimus to provide guidance for their coadministration. METHODS: In this open-label, single-sequence, crossover study, 12 healthy subjects received a single oral 4-mg dose of everolimus alone and again after an 8-day pretreatment with rifampin 600 mg/d. Urinary excretion of 6β-hydroxycortisol was measured at various time points during rifampin treatment as a marker of CYP3A4 induction. RESULTS: Urine excretion of 6β-hydroxycortisol was significantly elevated during treatment with rifampin compared with prestudy, indicating enzyme induction. When everolimus was coadministered during rifampin treatment, the apparent clearance of everolimus was significantly increased, on average by 172%. This was manifested as a decrease in maximum concentration in all subjects, on average by 58% (range 14–73%). The AUC remained unaffected in 1 subject (although 6β-hydroxycortisol indicated enzyme induction) and decreased in the other 11 subjects. The average decrease in AUC in the full study population was 63% (range 0–82%). Everolimus half-life was reduced significantly, from an average of 32 hours to 24 hours. CONCLUSIONS: In everolimus-treated patients for whom rifampin is indicated, alternative agents with less enzyme induction potential than rifampin could be considered. Alternatively, the dose of everolimus could be individually titrated based on everolimus therapeutic drug monitoring during rifampin therapy.

Host enzyme induction of bacterial infection

1968 ◽  
Vol 121 (1) ◽  
pp. 11-16 ◽  
Author(s):  
M. I. Rapoport
Keyword(s):  
Bacterial Infection ◽  
Enzyme Induction

Hypoxic metabolism in wild rice (Zizania palustris): enzyme induction and metabolite production

1993 ◽  
Vol 89 (1) ◽  
pp. 165-171 ◽  
Author(s):  
Douglas G. Muench ◽  
O. William Archibold ◽  
Allen G. Good
Keyword(s):  
Enzyme Induction ◽  
Wild Rice ◽  
Metabolite Production ◽  
Zizania Palustris

scholarly journals Carbohydrate Repression of Enzyme Induction in Rat Liver

1963 ◽  
Vol 238 (5) ◽  
pp. PC1910-PC1912
Author(s):  
Henry C. Pitot ◽  
Carl Peraino
Keyword(s):  
Rat Liver ◽  
Enzyme Induction

scholarly journals Conversion of Daidzein and Genistein by an Anaerobic Bacterium Newly Isolated from the Mouse Intestine

2008 ◽  
Vol 74 (15) ◽  
pp. 4847-4852 ◽  
Author(s):  
Anastasia Matthies ◽  
Thomas Clavel ◽  
Michael Gütschow ◽  
Wolfram Engst ◽  
Dirk Haller ◽  
...  
Keyword(s):  
Stationary Phase ◽  
Enzyme Induction ◽  
Growth Phase ◽  
Anaerobic Bacterium ◽  
Stationary Growth Phase ◽  
Gut Bacteria ◽  
Soy Isoflavones ◽  
Strictly Anaerobic ◽  
Stationary Growth ◽  
Mouse Intestine

ABSTRACT The metabolism of isoflavones by gut bacteria plays a key role in the availability and bioactivation of these compounds in the intestine. Daidzein and genistein are the most common dietary soy isoflavones. While daidzein conversion yielding equol has been known for some time, the corresponding formation of 5-hydroxy-equol from genistein has not been reported previously. We isolated a strictly anaerobic bacterium (Mt1B8) from the mouse intestine which converted daidzein via dihydrodaidzein to equol as well as genistein via dihydrogenistein to 5-hydroxy-equol. Strain Mt1B8 was a gram-positive, rod-shaped bacterium identified as a member of the Coriobacteriaceae. Strain Mt1B8 also transformed dihydrodaidzein and dihydrogenistein to equol and 5-hydroxy-equol, respectively. The conversion of daidzein, genistein, dihydrodaidzein, and dihydrogenistein in the stationary growth phase depended on preincubation with the corresponding isoflavonoid, indicating enzyme induction. Moreover, dihydrogenistein was transformed even more rapidly in the stationary phase when strain Mt1B8 was grown on either genistein or daidzein. Growing the cells on daidzein also enabled conversion of genistein. This suggests that the same enzymes are involved in the conversion of the two isoflavones.

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