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Effect of Body Weight and Age on the Pharmacokinetics of Dihydroartemisinin: FDA Basis for Dose Determination of Artesunate for Injection in Pediatric Patients with Severe Malaria

February 23, 2021 - 12:48 -- Open Access
Kitabi E, Bensman TJ, Earp JC, Chilukuri DM, Smith H, Ball L, O'Shaughnessy E, Yasinskaya Y, Colangelo PM, Reynolds KS
Clin Infect Dis. 2021 Feb 19:ciab149

For treatment of severe malaria, the WHO recommends 3 mg/kg intravenous artesunate in pediatric patients weighing less than 20 kg.

NOT Open Access | Dihydroartemisinin, an active metabolite of artemisinin, interferes with Leishmania braziliensis mitochondrial bioenergetics and survival

January 12, 2021 - 14:55 -- NOT Open Access
Grazzia N, Boaventura S Jr, Garcia VL, Gadelha FR, Miguel DC
Parasitol Res. 2021 Jan 8

Leishmaniasis is one of the most neglected parasitic infections of the world and current therapeutic options show several limitations. In the search for more effective drugs, plant compounds represent a powerful natural source. Artemisinin is a sesquiterpene lactone extracted from Artemisia annua L. leaves, from which dihydroartemisinin (DQHS) and artesunic acid (AA)/artesunate are examples of active derivatives.

NOT Open Access | Predicting the Disposition of the Antimalarial Drug Artesunate and its Active Metabolite Dihydroartemisinin Using Physiologically-Based Pharmacokinetic Modeling

December 29, 2020 - 15:33 -- NOT Open Access
Arey R, Reisfeld B
Antimicrob Agents Chemother. 2020 Dec 23:AAC.02280-20

Artemisinin-based combination therapies (ACTs) have proven to be effective in helping to combat the global malaria epidemic. To optimally apply these drugs, information about their tissue-specific disposition is required, and one approach to predict these pharmacokinetic characteristics is physiologically-based pharmacokinetic (PBPK) modeling. In this study, a whole-body PBPK model was developed to simulate the time-dependent tissue concentrations of artesunate (AS) and its active metabolite, dihydroartemisinin (DHA).

Mass Drug Administration With High-Dose Ivermectin and Dihydroartemisinin-Piperaquine for Malaria Elimination in an Area of Low Transmission With High Coverage of Malaria Control Interventions: Protocol for the MASSIV Cluster Randomized Clinical Trial

November 25, 2020 - 12:10 -- Open Access
Dabira ED, Soumare HM, D'Alessandro U, et al.
JMIR Res Protoc. 2020 Nov 19;9(11):e20904

With a decline in malaria burden, innovative interventions and tools are required to reduce malaria transmission further. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) has been identified as a potential tool to further reduce malaria transmission, where coverage of vector control interventions is already high. However, the impact is limited in time. Combining an ACT with an endectocide treatment that is able to reduce vector survival, such as ivermectin (IVM), could increase the impact of MDA and offer a new tool to reduce malaria transmission.

NOT Open Access | Artemisinin-type drugs for the treatment of hematological malignancies

November 4, 2020 - 15:11 -- NOT Open Access
Mancuso RI, Foglio MA, Olalla Saad ST
Cancer Chemother Pharmacol. 2020 Nov 3

Qinghaosu, known as artemisinin (ARS), has been for over two millennia, one of the most common herbs prescribed in traditional Chinese medicine (TCM). ARS was developed as an antimalarial drug and currently belongs to the established standard treatments of malaria as a combination therapy worldwide. In addition to the antimalarial bioactivity of ARS, anticancer activities have been shown both in vitro and in vivo.

Artemisinin exposure at the ring or trophozoite stage impacts Plasmodium falciparum sexual conversion differently

October 22, 2020 - 15:52 -- Open Access
Portugaliza HP, Miyazaki S, Geurten FJ, Pell C, Rosanas-Urgell A, Janse CJ, Cortés A
Elife. 2020 Oct 21;9:e60058

Malaria transmission is dependent on the formation of gametocytes in the human blood. The sexual conversion rate, the proportion of asexual parasites that convert into gametocytes at each multiplication cycle, is variable and reflects the relative parasite investment between transmission and maintaining the infection. The impact of environmental factors such as drugs on sexual conversion rates is not well understood.

Tolerance of Gambian Plasmodium falciparum to Dihydroartemisinin and Lumefantrine detected by Ex vivo Parasite Survival Rate Assay (PSRA)

October 7, 2020 - 15:39 -- Open Access
Mbye H, Bojang F, Jawara AS, Njie B, Mohammed NI, Okebe J, D'Alessandro U, Amambua-Ngwa A
Antimicrob Agents Chemother. 2020 Oct 5:AAC.00720-20

Monitoring of Plasmodium falciparum sensitivity to antimalarial drugs in Africa is vital for malaria elimination. However, the commonly used ex-vivo/in-vitro IC50 test is inconsistent for several antimalarials, while the alternative ring-stage survival assay (RSA) for artemisinin derivatives has not been widely adopted. Here we applied an alternative two-colour flow-cytometry based parasite survival rate assay (PSRA) to detect ex-vivo antimalarial tolerance in P. falciparum isolates from The Gambia.

Antimalarial drugs inhibit the replication of SARS-CoV-2: an in vitro evaluation

September 15, 2020 - 14:26 -- Open Access
Gendrot M, Andreani J, Pradines B, et al.
Travel Med Infect Dis. 2020 Sep 8:101873

In December 2019, a new severe acute respiratory syndrome coronavirus (SARS-CoV-2) causing coronavirus diseases 2019 (COVID-19) emerged in Wuhan, China. African countries see slower dynamic of COVID-19 cases and deaths. One of the assumptions that may explain this later emergence in Africa, and more particularly in malaria endemic areas, would be the use of antimalarial drugs.

NOT Open Access | A combined Raman optical activity and vibrational circular dichroism study on artemisinin-type products

August 10, 2020 - 14:34 -- NOT Open Access
Bogaerts J, Desmet F, Aerts R, Bultinck P, Herrebout W, Johannessen C
Phys Chem Chem Phys. 2020 Aug 5

Artemisinin and two of its derivatives, dihydroartemisinin and artesunate, which are front line drugs against malaria, were investigated using Raman optical activity (ROA) and vibrational circular dichroism (VCD) experiments, both supported by density functional theory (DFT) level calculations. The experimental techniques combined with DFT calculations could show that dihydroartemisinin was present as an epimeric mixture in solution.

NOT Open Access | Dihydroartemisinin exposure impairs porcine ovarian granulosa cells by activating PERK-eIF2α-ATF4 through endoplasmic reticulum stress

July 30, 2020 - 07:14 -- NOT Open Access
Luo Y, Guo Q, Zhang L, Zhuan Q, Meng L, Fu X, Hou Y
Toxicol Appl Pharmacol. 2020 Jul 25:115159

Dihydroartemisinin (DHA) is an artemisinin derivative commonly used in malaria therapy, and a growing number of studies have focused on the potent anticancer activity of DHA. However, the reproductive toxicity of anticancer drugs is a major concern for young female cancer patients. Previous studies have suggested that DHA can cause embryonic damage and affect oocyte maturation.


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