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- Svensson, Ulrika S H, et al.
(författare)
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Artemisinin induces omeprazole metabolism in human beings
- 1998
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Ingår i: Clinical Pharmacology and Therapeutics. - 0009-9236 .- 1532-6535. ; 64, s. 160-
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study investigated whether time-dependent artemisinin pharmacokinetics correlated to CYP3A4 or CYP2C19 activity in vivo. Methods: Artemisinin (two oral doses per day of 250 mg) was given to nine healthy Vietnamese subjects for 7 days (day 1 to day 7), Single 20 mg doses of omeprazole were given orally on day -7, day 1, and day 7, Single doses of artemisinin and omeprazole were given in combination on day 14 after a 6-day washout period. The pharmacokinetics of artemisinin, omeprazole, hydroxyomeprazole, and omeprazole sulfone were evaluated on days -7, 1, 7, and 14, On the same days urine was collected for the determination of 6 beta-hydroxycortisol and cortisol excretion. Results: Areas under plasma concentration-time curves (AUC) for artemisinin and omeprazole decreased on day 7 to 20% (95% confidence intervals, 13%, 28%) and 35% (25%, 46%), respectively, compared with values on day 1, AUC ratios for hydroxyomeprazole/omeprazole increased 2.2-fold (1,7, 2.7) on day 7 compared with values on day 1, Al values were normalized at day 14, There were no significant changes in the omeprazole sulfone/omeprazole ratio or in the 6 beta-hydroxycortisol/cortisol ratio between the study days. In one subject found to have poor CYP2C19 metabolization, the elimination of omeprazole increased after artemisinin exposure, with no change in the hydroxyomeprazole/omeprazole AUC ratio. Conclusion: Artemisinin did not alter CYP3A4 activity, whereas an increase in CYP2C19 activity was observed. The increased elimination of omeprazole in both poor and extensive CYP2C19 metabolizers suggests artemisinin induces both CYP2C19 and another enzyme.
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- Wadelius, Mia, et al.
(författare)
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Induction of CYP2D6 in pregnancy
- 1997
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Ingår i: Clinical Pharmacology and Therapeutics. - 0009-9236 .- 1532-6535. ; 62:4, s. 400-7
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Tidskriftsartikel (refereegranskat)abstract
- Expression of the drug-metabolizing enzyme cytochrome P4502D6 (CYP2D6) is predominantly under genetic control, and enzyme-inducing drugs have little influence on its activity. We studied the activity of CYP2D6 during pregnancy. One hundred forty pregnant women were genotyped for CYP2D6. Seventeen of them (four poor metabolizers, seven heterozygous extensive metabolizers, and six extensive metabolizers) were phenotyped with dextromethorphan in late pregnancy and 7 to 11 weeks after parturition. During pregnancy the dextromethorphan/dextrorphan metabolic ratio was significantly reduced (p = 0.0015) among homozygous and heterozygous extensive metabolizers, indicating increased CYP2D6 activity. In contrast, poor metabolizers showed an increased metabolic ratio during pregnancy. These results are consistent with previous findings of a marked increase in metabolism of the CYP2D6 substrate metoprolol during pregnancy. Both studies indicate an increase in CYP2D6 activity during pregnancy, which may be caused by an induction of the CYP2D6 enzyme.
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