| 1. |
- Gordi, Toufigh, et al.
(författare)
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Artemisinin pharmacokinetics and efficacy in uncomplicated-malaria patients treated with two different dosage regimens.
- 2002
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Ingår i: Antimicrobial agents and chemotherapy. - 0066-4804. ; 46:4, s. 1026-31
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Tidskriftsartikel (refereegranskat)abstract
- The immediate efficacies of two oral dosage regimens of artemisinin were investigated in 77 male and female adult Vietnamese falciparum malaria patients randomly assigned to treatment with either 500 mg of artemisinin daily for 5 days (group A; n = 40) or artemisinin at a dose of 100 mg per day for 2 days, with the dose increased to 250 mg per day for 2 consecutive days and with a final dose of 500 mg on the fifth day (group B; n = 37). Parasitemia was monitored every 4 h. The average parasite clearance time was longer in group B than in group A (means +/- standard deviations, 50 +/- 23 and 34 +/- 14 h, respectively; P < 0.01). Artemisinin concentrations in saliva samples obtained on days 1 and 5 were quantified by high-performance liquid chromatography. The average oral clearance, based on saliva drug concentrations in group B patients, was twofold higher than that in group A patients on day 1 (P < 0.01), with no differences in drug half-lives (P = 0.40), indicating a saturable first-pass metabolism. Female patients had higher oral clearance values on day 1. Artemisinin's pharmacokinetic parameters were similar on day 5 in both groups, although a significant increase in oral clearance from day 1 to day 5 was evident. Thus, artemisinin exhibited both dose- and time-dependent pharmacokinetics. The escalating dose studied did not result in higher artemisinin concentrations toward the end of the treatment period.
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| 2. |
- Hai, Trinh Ngoc, et al.
(författare)
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The influence of food on the pharmacokinetics of piperaquine in healthy Vietnamese volunteers.
- 2008
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Ingår i: Acta tropica. - : Elsevier BV. - 0001-706X. ; 107:2, s. 145-9
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Tidskriftsartikel (refereegranskat)abstract
- The combination piperaquine and dihydroartemisinin is emerging as first line treatment of uncomplicated falciparum malaria in Southeast Asia. The aim of this study was to determine the influence of a standard Vietnamese meal on the single-dose pharmacokinetics of piperaquine when administered in combination with dihydroartemisinin, and to gain extended data on the terminal half-life of piperaquine in healthy Vietnamese volunteers. Subjects were randomly assigned to take a single oral dose of piperaquine phosphate (640 mg)+dihydroartemisinin (80 mg) together with a standardized Vietnamese meal (n=16) or to remain fasting for 4h following drug intake (n=16). Frequent blood sampling was conducted during 36 h, followed by weekly samples for 7 weeks. The pharmacokinetic parameters of piperaquine were determined by noncompartmental analysis. The median (80% central range) AUC(0-last) was 11.5 (6.9-17.3)h mg/L in fed and 13.9 (2.8-19.3)h mg/L in fasting subjects, indicating a considerable variability in exposure in both groups. The estimated overall oral clearance was 0.27 (0.12-1.49)L/(h kg), the volume of distribution during the terminal elimination phase was 230 (102-419)L/kg and estimated terminal half-life was 18 (5-93) days. This study did not demonstrate a significant impact of a standardized Vietnamese meal on the oral absorption of piperaquine.
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| 3. |
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| 4. |
- Simonsson, Ulrika S H, et al.
(författare)
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Artemisinin autoinduction is caused by involvement of cytochrome P450 2B6 but not 2C9.
- 2003
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Ingår i: Clinical pharmacology and therapeutics. - 0009-9236 .- 1532-6535. ; 74:1, s. 32-43
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Tidskriftsartikel (refereegranskat)abstract
- Our goal was to investigate whether artemisinin autoinduction is caused by an increase in cytochrome P450 (CYP) 2B6 or CYP2C9 activities, we evaluated the effects of multiple-dose artemisinin administration on S-mephenytoin N-demethylation in healthy subjects.
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