Yeramian Patrick, Meshnick Steven R, Krudsood Srivicha, Chalermrut Kobsiri, Silachamroon Udomsak, Tangpukdee Noppadon, Allen James, Brun Reto, Kwiek Jesse J, Tidwell Richard, Looareesuwan Sornchai
Immtech International, Vernon Hills, Illinois, USA.
J Infect Dis. 2005 Jul 15;192(2):319-22. doi: 10.1086/430928. Epub 2005 Jun 7.
DB289 is the orally active prodrug of the diamidine DB75, which was developed for the treatment of human African trypanosomiasis.
We tested the safety and efficacy of DB289 for the treatment of Plasmodium vivax and acute, uncomplicated P. falciparum infections in an open-label pilot study at the Hospital for Tropical Diseases in Bangkok. Nine patients with P. vivax infections and 23 patients with P. falciparum infections were admitted and treated with 100 mg of DB289 given orally twice a day for 5 days and were followed for 28 days. Patients with P. vivax infections were also treated with primaquine on days 10-23.
All patients cleared parasites by day 7, with a mean+/-SD clearance time of 43+/-41 h. One patient with a P. vivax infection had a recurrence of parasitemia on day 9. Of the 23 patients with P. falciparum infections, 3 had recurrences of parasitemia caused by P. vivax and 2 had recurrences of parasitemia caused by P. falciparum. In only 1 of 2 recurrences of parasitemia caused by P. falciparum were the parasites genotypically distinct from the infecting parasites the patient had at enrollment, which means there was a 96% cure rate.
DB289 is a promising new antimalarial compound that could become an important component of new antimalarial combinations.
DB289是二脒DB75的口服活性前体药物，开发用于治疗人类非洲锥虫病。
在曼谷热带病医院进行的一项开放标签的试点研究中，我们测试了DB289治疗间日疟原虫和急性非复杂性恶性疟原虫感染的安全性和有效性。9例间日疟原虫感染患者和23例恶性疟原虫感染患者入院，每天口服100mg DB289，分两次服用，共5天，并随访28天。间日疟原虫感染患者在第10 - 23天也接受了伯氨喹治疗。
所有患者在第7天清除了寄生虫，平均清除时间为43±41小时（均值±标准差）。1例间日疟原虫感染患者在第9天出现了寄生虫血症复发。在23例恶性疟原虫感染患者中，3例出现了间日疟原虫引起的寄生虫血症复发，2例出现了恶性疟原虫引起的寄生虫血症复发。在恶性疟原虫引起的2次寄生虫血症复发中，只有1次复发的寄生虫在基因分型上与患者入组时感染的寄生虫不同，这意味着治愈率为96%。
DB289是一种有前景的新型抗疟化合物，可能成为新型抗疟联合用药的重要组成部分。
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