Passarell Julie, Ludwig Elizabeth, Liolios Kathryn, Meagher Alison K, Grasela Thaddeus H, Babinchak Timothy, Ellis-Grosse Evelyn J
Pharmacologic Division, Cognigen Corporation, Buffalo, NY 14221, USA.
Diagn Microbiol Infect Dis. 2009 Oct;65(2):123-9. doi: 10.1016/j.diagmicrobio.2009.06.019.
Tigecycline exposure (area under the concentration-time curve [AUC((0-infinity))] and maximum serum concentration [C(max)]) and first occurrence of nausea and vomiting were evaluated in 136 healthy subjects after 12.5- to 300-mg single doses. Nausea was more frequent in females (46%, 10/22) compared with males (31%, 11/36) after 100-mg doses. Most nausea (vomiting) events occurred < or =4 h (<6 h) after tigecycline. For doses < or =100 mg, the median duration of nausea and vomiting was approximately 5 h. Based on logistic regression, increased exposure (AUC((0-infinity)) >C(max)) to tigecycline results in an increased rate of nausea (P < or = .0001; = .0022) and vomiting (P < or = .0001; = .0006). At the median AUC((0-infinity)) (C(max)) for the 50-mg dose group, the probability of nausea and vomiting was 0.26 (0.29) and 0.07 (0.11), respectively. Model-predicted rates of nausea and vomiting were comparable with those observed for the tetracycline class of antibiotics, with tolerable rates predicted after 50-mg doses of tigecycline.
在136名健康受试者单次服用12.5至300毫克替加环素后，评估了替加环素暴露量（浓度-时间曲线下面积[AUC((0-无穷大))]和血清最大浓度[C(max)]）以及恶心和呕吐首次出现的情况。服用100毫克剂量后，女性恶心的发生率（46%，10/22）高于男性（31%，11/36）。大多数恶心（呕吐）事件发生在替加环素给药后≤4小时（<6小时）。对于≤100毫克的剂量，恶心和呕吐的中位持续时间约为5小时。基于逻辑回归分析，替加环素暴露量增加（AUC((0-无穷大))>C(max)）会导致恶心发生率增加（P≤.0001；=.0022）和呕吐发生率增加（P≤.0001；=.0006）。在50毫克剂量组的中位AUC((0-无穷大))（C(max)）时，恶心和呕吐的概率分别为0.26（0.29）和0.07（0.11）。模型预测的恶心和呕吐发生率与四环素类抗生素观察到的发生率相当，50毫克剂量的替加环素预测的发生率可耐受。
