Comparison of the Pharmacokinetics and Ex Vivo Antimalarial Activities of Artesunate–Amodiaquine and Artemisinin–Piperaquine in Healthy Volunteers for Preselection Malaria Therapy
| Autor: | Kerryn Rowcliffe, Karin van Breda, Nguyen Ngoc Quang, Geoffrey W. Birrell, Chu Xuan Anh, Marina Chavchich, Thomas Travers, Michael D. Edstein |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_treatment 030231 tropical medicine 030106 microbiology Plasmodium falciparum Dihydroartemisinin Pharmacology Drug Administration Schedule 03 medical and health sciences Antimalarials Young Adult 0302 clinical medicine Parasitic Sensitivity Tests In vivo Virology Piperaquine parasitic diseases medicine Humans Artemisinin Malaria Falciparum Active metabolite Biotransformation biology business.industry Artesunate/amodiaquine Amodiaquine Articles biology.organism_classification Artemisinins Healthy Volunteers Drug Combinations Infectious Diseases Area Under Curve Quinolines Parasitology business Ex vivo medicine.drug Half-Life Tablets |
| Popis: | The pharmacokinetics (PK) and ex vivo activity (pharmacodynamics [PD]) of two artemisinin combination therapies (ACTs) (artemisinin–piperaquine [ARN–PPQ] [Artequick(®)] and artesunate–amodiaquine [ARS–AQ] [Coarsucam(™)]) in healthy Vietnamese volunteers were compared following 3-day courses of the ACTs for the preselection of the drugs for falciparum malaria therapy. For PK analysis, serial plasma samples were collected from two separate groups of 22 volunteers after ACT administration. Of these volunteers, ex vivo activity was assessed in plasma samples from seven volunteers who received both ACTs. The area under the concentration–time curve (AUC(0–∞)) was 3.6-fold higher for dihydroartemisinin (active metabolite of ARS) than that for ARN, whereas the AUC(0–∞) of desethylamodiaquine (active metabolite of AQ) was 2.0-fold lower than that of PPQ. Based on the 50% inhibitory dilution values of the volunteers’ plasma samples collected from 0.25 to 3 hours after the last dose, the ex vivo activity of ARS–AQ was 2.9- to 16.2-fold more potent than that of ARN–PPQ against the drug-sensitive D6 Plasmodium falciparum line. In addition, at 1.5, 4.0, and 24 hours after the last dose, the ex vivo activity of ARS–AQ was 20.8-, 3.5-, and 8.5-fold more potent than that of ARN–PPQ against the ARN-sensitive MRA1239 line. By contrast, at 1.5 hours, the ex vivo activity of ARS–AQ was 5.4-fold more active than that of ARN–PPQ but had similar activities at 4 and 24 hours against the ARN-resistant MRA1240 line. The PK–PD data suggest that ARS–AQ possesses superior antimalarial activity than that of ARN–PPQ and would be the preferred ACT for further in vivo efficacy testing in multidrug-resistant falciparum malaria areas. |
| Databáze: | OpenAIRE |
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