Comparative study of dihydroartemisinin and artesunate safety in healthy Thai volunteers
Objective: As part of new drug development initiatives in Thailand, a new tablet formulation of dihydroartemisinin (DHA, an antimalarial drug) has been developed. Our previous bioequivalence study indicated that the new and reference DHA formulations were well tolerated; however, a significant decre...
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th-mahidol.282572018-09-13T14:13:36Z Comparative study of dihydroartemisinin and artesunate safety in healthy Thai volunteers S. Kongpatanakul S. Chatsiricharoenkul A. Khuhapinant S. Atipas J. Kaewkungwal Mahidol University Medicine Pharmacology, Toxicology and Pharmaceutics Objective: As part of new drug development initiatives in Thailand, a new tablet formulation of dihydroartemisinin (DHA, an antimalarial drug) has been developed. Our previous bioequivalence study indicated that the new and reference DHA formulations were well tolerated; however, a significant decrease in hemoglobin was detected after a single 200-mg oral dose. To explore further, a clinical study with an emphasis on hematological parameters was conducted. Methods: A single-center, randomized, single-blind, cross-over clinical study was conducted in 18 healthy volunteers with a dosage of 300 mg daily for 2 days. Artesunate was used as a comparator. Adverse events were monitored and laboratory parameters on study Days 0, 2, 5, and 7 post drug administrations were analyzed. Results: Eighteen volunteers completed both rounds of the study. Both drugs were well tolerated. All adverse events were mild. Significant decrease in hemoglobin compared to baseline was detected for both drugs 7 days after administration (DHA: 0.48 g/dl, p = 0.007; artesunate 0.38 g/dl, p = 0.001). Transient bone marrow suppression was evidenced by reduction of reticulocytes with a lowest number on study Day 5 (artesunate 75% reduction in reticulocyte count; DHA47%, p <0.001 for both drugs compared to baseline). Conclusion: The present study confirmed our previous finding on significant decrease in hemoglobin. Artesunate appeared to have more negative effects on the numbers of reticulocytes and white blood cells than DHA. Systemic laboratory and toxicity profiles presented in this study may be used as a framework for future clinical studies of artemisinin and its derivatives. © 2009 Dustri-Verlag Dr. K. Feistle. 2018-09-13T07:07:42Z 2018-09-13T07:07:42Z 2009-01-01 Article International Journal of Clinical Pharmacology and Therapeutics. Vol.47, No.9 (2009), 579-586 10.5414/CPP47579 09461965 2-s2.0-70349899121 https://repository.li.mahidol.ac.th/handle/123456789/28257 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=70349899121&origin=inward |
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Medicine Pharmacology, Toxicology and Pharmaceutics S. Kongpatanakul S. Chatsiricharoenkul A. Khuhapinant S. Atipas J. Kaewkungwal Comparative study of dihydroartemisinin and artesunate safety in healthy Thai volunteers |
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Objective: As part of new drug development initiatives in Thailand, a new tablet formulation of dihydroartemisinin (DHA, an antimalarial drug) has been developed. Our previous bioequivalence study indicated that the new and reference DHA formulations were well tolerated; however, a significant decrease in hemoglobin was detected after a single 200-mg oral dose. To explore further, a clinical study with an emphasis on hematological parameters was conducted. Methods: A single-center, randomized, single-blind, cross-over clinical study was conducted in 18 healthy volunteers with a dosage of 300 mg daily for 2 days. Artesunate was used as a comparator. Adverse events were monitored and laboratory parameters on study Days 0, 2, 5, and 7 post drug administrations were analyzed. Results: Eighteen volunteers completed both rounds of the study. Both drugs were well tolerated. All adverse events were mild. Significant decrease in hemoglobin compared to baseline was detected for both drugs 7 days after administration (DHA: 0.48 g/dl, p = 0.007; artesunate 0.38 g/dl, p = 0.001). Transient bone marrow suppression was evidenced by reduction of reticulocytes with a lowest number on study Day 5 (artesunate 75% reduction in reticulocyte count; DHA47%, p <0.001 for both drugs compared to baseline). Conclusion: The present study confirmed our previous finding on significant decrease in hemoglobin. Artesunate appeared to have more negative effects on the numbers of reticulocytes and white blood cells than DHA. Systemic laboratory and toxicity profiles presented in this study may be used as a framework for future clinical studies of artemisinin and its derivatives. © 2009 Dustri-Verlag Dr. K. Feistle. |
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Mahidol University |
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Mahidol University S. Kongpatanakul S. Chatsiricharoenkul A. Khuhapinant S. Atipas J. Kaewkungwal |
format |
Article |
author |
S. Kongpatanakul S. Chatsiricharoenkul A. Khuhapinant S. Atipas J. Kaewkungwal |
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S. Kongpatanakul |
title |
Comparative study of dihydroartemisinin and artesunate safety in healthy Thai volunteers |
title_short |
Comparative study of dihydroartemisinin and artesunate safety in healthy Thai volunteers |
title_full |
Comparative study of dihydroartemisinin and artesunate safety in healthy Thai volunteers |
title_fullStr |
Comparative study of dihydroartemisinin and artesunate safety in healthy Thai volunteers |
title_full_unstemmed |
Comparative study of dihydroartemisinin and artesunate safety in healthy Thai volunteers |
title_sort |
comparative study of dihydroartemisinin and artesunate safety in healthy thai volunteers |
publishDate |
2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/28257 |
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1763495582781931520 |