{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T11:14:08Z","timestamp":1759058048841},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,10,22]],"date-time":"2009-10-22T00:00:00Z","timestamp":1256169600000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research Pt B"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Artesunate (AS), a rapid, effective, and safe antimalarial drug, has been used for the treatment of malaria for decades. However, severe embryolethality was found for injectable AS in pregnant animals. In the present study, pregnant rats were selected and dosed with AS (GMP product) intravenously (IV) and intramuscularly (IM) at varied doses daily for 13 days from gestation day (GD) 6 to 18. In addition, a toxic dose of 1.2\u2009mg\/kg\/day was subsequently tested in the GD 6\u201310, GD 11\u201315, and GD 16\u201320 periods of rat pregnancy. A pharmacokinetic study was also conducted to evaluate the bioavailability of AS following the IM administrations. Results showed that no significant adverse effects were found in maternal rats. All of the fetuses were either damaged or reabsorbed by placentas in treated pregnant rats, but doses did not show an adverse effect at 0.4 and 0.5\u2009mg\/kg after IV and IM administrations, respectively. The survival rate of fetuses is dose\u2010dependent and the 50% fetus re\u2010absorption doses (FRD<jats:sub>50<\/jats:sub>) were 0.61 and 0.60\u2009mg\/kg following the IV and IM, respectively. The most drug\u2010sensitive period, showing severe embryotoxicity, was between GD 11 and 15 for injectable AS. When calculated with total concentrations of AS and dihydroartemisinin, an active metabolite of AS, the bioavailability of 97.8% after intramuscular injection was fulfilled to a bioequivalence of that in intravenous treatment. The fact that injectable AS exhibited severe embryolethality after both IV and IM injections seems related to their comparable pharmacokinetic profiles that indicate high peak concentrations in pregnant animals. <jats:italic>Birth Defects Res (Part B)<\/jats:italic> 86:385\u2013393, 2009. Published 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdrb.20207","type":"journal-article","created":{"date-parts":[[2009,10,22]],"date-time":"2009-10-22T14:42:57Z","timestamp":1256222577000},"page":"385-393","source":"Crossref","is-referenced-by-count":14,"title":["Severe embryolethality of artesunate related to pharmacokinetics following intravenous and intramuscular doses in pregnant rats"],"prefix":"10.1002","volume":"86","author":[{"given":"Qigui","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanzheng","family":"Si","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Weina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,10,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2005.09.019"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1998.00655.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1997.56.17"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2007.11.003"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.5.2.199"},{"key":"e_1_2_6_7_1","first-page":"118","article-title":"Embryotoxicity and teratogenicity studies on artemether in mice, rats and rabbits","volume":"5","author":"Chen LJ","year":"1984","journal-title":"Zhongguo Yao Li Xue Bao"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000076256"},{"key":"e_1_2_6_9_1","first-page":"31","article-title":"Studies on the toxicity of qinghaosu and its derivatives","volume":"2","author":"China Cooperative Research Group on qinghaosu and its derivatives as antimalarials","year":"1982","journal-title":"J Tradit Chin Med"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20027"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20165"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20163"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7801115"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2007.08.084"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/beog.2001.0231"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000094521"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0300-483X(90)90081-Q"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-007-9030-8"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/15287399009531428"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/10915810591007201"},{"key":"e_1_2_6_21_1","doi-asserted-by":"crossref","first-page":"817","DOI":"10.4269\/ajtmh.2006.75.817","article-title":"The evaluation of radiolabeled artesunate on tissue distribution in rats and protein binding in humans","volume":"75","author":"Li Q","year":"2006","journal-title":"Am J Trop Med Hyg"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.20380"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20164"},{"key":"e_1_2_6_24_1","first-page":"42","article-title":"Teratogenicity of sodium artesunate","volume":"13","author":"Li ZL","year":"1988","journal-title":"Zhong Yao Tong Bao"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2006.08.001"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2005.05.005"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-003-0652-9"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1086\/432551"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0050253"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(96)00505-1"},{"key":"e_1_2_6_31_1","first-page":"CD004912","article-title":"Drugs for treating uncomplicated malaria in pregnant women","volume":"20","author":"Orton L","year":"2005","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20502"},{"key":"e_1_2_6_33_1","unstructured":"US Food and Drug Administration.2002. 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