Sanders Madeline, Hong Eunjin, Chung Peter S, Rao Adupa P, Beringer Paul
Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA.
College of Pharmacy, CHA University, Seongnam-si, South Korea.
Clin Pharmacokinet. 2024 Dec;63(12):1701-1709. doi: 10.1007/s40262-024-01440-w. Epub 2024 Nov 24.
Omadacycline offers a potential advancement in the management of infections in people with cystic fibrosis (CF) because of its spectrum of activity, intrapulmonary penetration, and oral bioavailability. A prospective single-dose, single-arm study was conducted to characterize the pharmacokinetic (PK) profile of omadacycline in people with CF, considering the known alterations in PK observed in this population (NCT04460586, 2020-07-01).
Plasma samples were obtained from nine adults with CF who received a single dose of intravenous omadacycline 100 mg over 0.5 h followed by a 1-week washout and an oral dose of omadacycline 300 mg. The data were analyzed using noncompartmental PK.
The maximum plasma concentration (C) and area under the curve extrapolated to infinity (AUC) after intravenous administration of omadacycline were similar between healthy volunteers and people with CF. The absorption kinetics of oral omadacycline, encompassing both the rate (C and time to C [t]) and the extent (AUC), also showed consistency between healthy volunteers and people with CF. The absolute bioavailability of the oral tablet formulation of omadacycline in people with CF (31.2%) was also consistent with that observed in healthy volunteers (34.5%). In comparing the two routes of administration, intravenous omadacycline 100 mg provided plasma exposures equivalent to those with oral omadacycline 300 mg in people with CF, as evidenced by geometric mean ratios for both AUC (0.9381; 90% confidence intervals [CI] 0.6783-1.2975) and C (0.7746; 90% CI 0.5478-1.0951).
Overall, the similarity in plasma PK observed in this study when comparing healthy volunteers and infected patients indicates that no dosing alterations are necessary when using omadacycline in people with CF.
奥马环素因其抗菌谱、肺内渗透性和口服生物利用度，为囊性纤维化（CF）患者感染的管理提供了潜在进展。开展了一项前瞻性单剂量、单臂研究，以描述奥马环素在CF患者中的药代动力学（PK）特征，同时考虑到该人群中已知的PK改变（NCT04460586，2020年7月1日）。
从9名成年CF患者中采集血浆样本，这些患者接受了单次静脉注射100mg奥马环素，持续0.5小时，随后经过1周的洗脱期，再口服300mg奥马环素。使用非房室PK分析数据。
健康志愿者和CF患者静脉注射奥马环素后的最大血浆浓度（Cmax）和外推至无穷大的曲线下面积（AUC∞）相似。口服奥马环素的吸收动力学，包括速率（Cmax和达峰时间[tmax]）和程度（AUC），在健康志愿者和CF患者之间也表现出一致性。奥马环素口服片剂制剂在CF患者中的绝对生物利用度（31.2%）也与在健康志愿者中观察到的一致（34.5%）。比较两种给药途径时，静脉注射100mg奥马环素在CF患者中提供的血浆暴露量与口服300mg奥马环素相当，AUC的几何平均比值（0.938；90%置信区间[CI]0.6783 - 1.2975）和Cmax（0.7746；90%CI0.5478 - 1.0951）均证明了这一点。
总体而言，本研究中健康志愿者和感染患者血浆PK的相似性表明，CF患者使用奥马环素时无需调整剂量。
