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Echinostoma
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Aleksandra Oliveira-Menezes, Júlia Peralta Gonçalves
Many groups have proposed Echinostoma spp. rodent models to study anthelmintic drugs. The rodent life cycle in the laboratory is relatively simple, and this model produces rapid results.117 Gonçalves et al.15 highlighted that E. paraensei may constitute a good model with which to investigate new anthelmintic drugs, and indeed, several compounds have been tested in E. caproni in recent years. Keiser et al.106 showed the effect of in vivo and in vitro treatment of E. caproni with artemisinin, artemether, artemether, artesunate, and dihydroartemsinin. In this study, dihydroartemisinin was the fastest acting compound among artemisinins, and these compounds were not effective in reducing the worm burden after in vivo treatment. The 100% worm burden reductions were observed following administration of higher doses of artesunate or artemether.106 In another study, antimalarial 1,2,4-trioxolanes (OZs) were tested in E. caproni–mouse model, and similar to the artemisinins high doses of OZ78 were required to achieve a 100% worm burden reduction in E. caproni–infected mice.118
A
Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
Human liver microsomes metabolise artemether to the biologically active main metabolite dihydroartemisinin (demethylation), predominantly through the isoenzyme CYP3A4/5. Dihydroartemisinin is further converted to inactive metabolites.
Treatment and prevention of malaria
Published in David A Warrell, Herbert M Gilles, Essential Malariology, 2017
David A Warrell, William M Watkins, Peter A Winstanley
Extreme difficulties in analysis have hampered the pharmacokinetic study of the artemisinin compounds (White, 1985). Artemisinin and its derivatives are rapidly hydrolysed in vivo to dihydroartemisinin (DHA), the most potent of the artemisinins. Artemisinin and its derivatives are rapidly metabolized by the liver and have short elimination half-lives. Artemether absorption is slower, more variable and with lower biotransformation to DHA when administered by the intramuscular or intravenous routes in comparison to oral dosage.
The preclinical discovery and development of rectal artesunate for the treatment of malaria in young children: a review of the evidence
Published in Expert Opinion on Drug Discovery, 2021
Laís Pessanha de Carvalho, Andrea Kreidenweiss, Jana Held
Artesunate is the most therapeutically versatile artemisinin derivative and can be administered by intravenous, intramuscular, oral, or rectal routes [27]. Pharmacokinetic studies were performed in healthy volunteers (adults) or patients with malaria (children and adults) and the results of these different studies are summarized in Table 1 reviewed by Morris and collaborators [28]. When artesunate is given intravenously it reaches high plasma concentration (Cmax), declines rapidly and has consequently a short half-life of less than 15 min. After oral administration, the time to reach the maximum concentration (Tmax) is around 1 h, with a half-life ranging from 21 to 72 min. Pharmacokinetics of the rectal route is similar to the oral administration, but with a delayed maximal concentration and a longer artesunate half-life. Dihydroartemisinin is the active metabolite of artesunate and also all other artemisinins. Tmax of dihydroartemisinin lags behind and the half-life is also slightly longer (see Table 1). However, for the rectal administration the lag between artesunate and dihydroartemisinin is not as pronounced as with the oral administration, as no first-pass effect (rapid metabolism of a compound by the liver/gut before reaching the circulation) takes place.
What dominates the changeable pharmacokinetics of natural sesquiterpene lactones and diterpene lactones: a review focusing on absorption and metabolism
Published in Drug Metabolism Reviews, 2021
Ziwei Yu, Ziqiang Chen, Qijuan Li, Ke Yang, Zecheng Huang, Wenjun Wang, Siyu Zhao, Huiling Hu
When rats and volunteers take artemisinin orally, artemisinin has a higher level of utilization in the human body and will experience a slower elimination (Birgersson et al. 2016; Dai et al. 2019). Caenorhabditis elegans CICC 40250 model was established to be the workable microbial metabolic scheme and produced the same deoxyartemisinin with metabolites of artemisinin in vivo. While dihydroartemisinin is only detected in mice (Ma, Sun, et al. 2019). After oral administration of ginkgolides in rats, these components showed higher bioavailability and prolonged T1/2 compared with dogs (Chen et al. 2013; Huang et al. 2014; Aa et al. 2018). Due to differences in gastrointestinal (GI) contents, the hydrolysis forms among species need to be considered (Aa et al. 2018). Besides, flavin-containing mono-oxygenases could disturb the metabolism of diosbulbin and the different expression level among species may have an impact (Yang et al. 2014). The difference in the metabolic profile of andrographolide in the liver microsomes of humans, monkeys, dogs, pigs, rats, and mice is related to the different catalytic efficiency of glucuronidation (Tian et al. 2015).
Development of R8 modified epirubicin–dihydroartemisinin liposomes for treatment of non-small-cell lung cancer
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Jing-Jing Liu, Wei Tang, Min Fu, Xiao-Qing Gong, Liang Kong, Xue-Min Yao, Ming Jing, Fu-Yi Cai, Xue-Tao Li, Rui-Jun Ju
Dihydroartemisinin, originally isolated from the traditional Chinese medicinal plant Artemisia annua, is a first-line antimalarial drug [20]. Recent studies have shown that dihydroartemisinin has antitumor effects and exhibits selective cytotoxicity on a variety of human tumors, including lung cancer [21]. The antitumor characteristics of dihydroartemisinin included the induction of apoptosis, regulation of tumor-related genes, blockage of angiogenesis and inhibition of metastasis [11]. Cell-penetrating peptides are a class of short peptides and can facilitate the cellular uptake of biomolecules. Arginine 8 (R8) is a promising ligand and possesses multi-functions including tumor targeting and tumor cell penetrating [22]. Although R8 has a non-specific affinity to lung cancer cells, R8 modified drug delivery systems can firstly be accumulated into tumor sits by EPR effect after systemic administration and then the antitumor drugs are transported into tumor cells via the penetrating effects of R8 [23]. In recent research, R8 modified liposomes were considered to be a potential anti-lung drug delivery system with negligible permanent damage to the cell membrane [24]. Meanwhile, R8 can effectively transport liposomes across the cell membrane to improve drug uptake in the liposomes.