From the Children's Hospital of Orange County, Orange, California.
University of California, Irvine, California.
Pediatr Infect Dis J. 2021 Apr 1;40(4):317-323. doi: 10.1097/INF.0000000000003030.
Infections with Gram-positive bacteria, including acute bacterial skin and skin structure infections (ABSSSIs), are common in children. We describe a single-dose pharmacokinetics and safety study of tedizolid phosphate, a new oxazolidinone under investigation for the treatment of ABSSSIs in children, in hospitalized participants 2 to <12 years of age.
This open-label, multicenter, phase 1 trial (NCT02750761) enrolled hospitalized children 2 to <12 years of age receiving treatment for a confirmed/suspected Gram-positive bacterial infection. Participants were stratified by age (2 to <6 years and 6 to <12 years) to receive a single oral or intravenous dose of tedizolid phosphate. Evaluations included safety and pharmacokinetics of tedizolid phosphate and its active metabolite, tedizolid. Palatability of the oral suspension was also evaluated.
Thirty-two participants were enrolled and received 3-6 mg/kg of study medication. For both routes of administration, tedizolid phosphate was rapidly converted to tedizolid; median time to maximum tedizolid plasma concentration was 1-2 hours after initiation of the 1-hour intravenous infusion and 2-3 hours after oral dosing. The tedizolid mean terminal half-life was 5-6 hours and 6-7 hours for the intravenous and oral administration groups, respectively. The oral tedizolid phosphate suspension demonstrated high bioavailability comparable to that of the parenteral administration. A single dose of intravenous or oral tedizolid phosphate was well tolerated; no unexpected safety findings were observed.
Pharmacokinetic and safety observations provide the information necessary for the continued development of tedizolid phosphate for the treatment of Gram-positive infections in children, particularly ABSSSIs.
包括急性细菌性皮肤和皮肤结构感染（ABSSSI）在内的革兰氏阳性菌感染在儿童中较为常见。我们描述了一种新型噁唑烷酮类药物替加环素磷酸盐的单剂量药代动力学和安全性研究，该药正在研究用于治疗儿童 ABSSSI。
这项开放标签、多中心、I 期临床试验（NCT02750761）招募了 2 至<12 岁因确诊/疑似革兰氏阳性菌感染而住院的儿童参与者。参与者按年龄（2 至<6 岁和 6 至<12 岁）分层，接受单剂量口服或静脉注射替加环素磷酸盐。评估包括替加环素磷酸盐及其活性代谢物替加环素的安全性和药代动力学。还评估了口服混悬液的口感。
共招募了 32 名参与者，并接受了 3-6mg/kg 的研究药物。对于两种给药途径，替加环素磷酸盐均迅速转化为替加环素；静脉 1 小时输注开始后 1-2 小时和口服后 2-3 小时达到替加环素血浆浓度的中位数。替加环素的平均终末半衰期分别为静脉和口服给药组的 5-6 小时和 6-7 小时。口服替加环素磷酸盐混悬液表现出与肠外给药相当的高生物利用度。静脉或口服给予单剂量替加环素磷酸盐均耐受良好；未观察到预期之外的安全性发现。
药代动力学和安全性观察结果为进一步开发替加环素磷酸盐治疗儿童革兰氏阳性感染，特别是 ABSSSI，提供了必要的信息。
