Exposure-response analyses of tigecycline tolerability in healthy subjects

Tigecycline exposure (area under the concentration-time curve [AUC(0-∞)] and maximum serum concentration [Cmax]) 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 ≤4 h (<6 h) after tigecycline. For doses ≤100 mg, the median duration of nausea and vomiting was approximately 5 h. Based on logistic regression, increased exposure (AUC(0-∞) > Cmax) to tigecycline results in an increased rate of nausea (P ≤ .0001; = .0022) and vomiting (P ≤ .0001; = .0006). At the median AUC(0-∞) (Cmax) 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.