Exposure-response analyses of tigecycline tolerability in healthy subjects.
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.
Passarell
Julie
J
Pharmacologic Division, Cognigen Corporation, Buffalo, NY 14221, USA. julie.passarell@cognigencorp.com
Ludwig
Elizabeth
E
Liolios
Kathryn
K
Meagher
Alison K
AK
Grasela
Thaddeus H
TH
Babinchak
Timothy
T
Ellis-Grosse
Evelyn J
EJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009325:Nausea / Q000139:chemically induced; D000078304:Tigecycline; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced; D055815:Young Adult
D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline