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Artemisinin induces...
Artemisinin induces omeprazole metabolism in human beings
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- Svensson, Ulrika S H (author)
- Uppsala universitet,Institutionen för farmaci,Institutionen för farmaceutisk biovetenskap,Farmakokinetik
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- Ashton, M (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmacokinetics and Drug Therapy
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Hai, T N (author)
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- Bertilsson, L (author)
- Karolinska Institutet
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Huong, D X (author)
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Van Huong, N (author)
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Nieu, N T (author)
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Sy, N D (author)
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Lykkesfeldt, J (author)
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Cong, L D (author)
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(creator_code:org_t)
- 1998
- 1998
- English.
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In: Clinical Pharmacology and Therapeutics. - 0009-9236 .- 1532-6535. ; 64, s. 160-
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https://doi.org/10.1...
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Abstract
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- 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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- ref (subject category)
- art (subject category)
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- By the author/editor
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Svensson, Ulrika ...
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Ashton, M
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Hai, T N
-
Bertilsson, L
-
Huong, D X
-
Van Huong, N
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show more...
-
Nieu, N T
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Sy, N D
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Lykkesfeldt, J
-
Cong, L D
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show less...
- Articles in the publication
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Clinical Pharmac ...
- Clin Pharmacol T ...
- By the university
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Uppsala University
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Karolinska Institutet