PMID- 32839218
OWN - NLM
STAT- MEDLINE
DCOM- 20210617
LR  - 20210617
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 64
IP  - 11
DP  - 2020 Oct 20
TI  - An Open-Label Study of the Impact of Hepatic Impairment on the Pharmacokinetics 
      and Safety of Single Oral and Intravenous Doses of Omadacycline.
LID - 10.1128/AAC.01650-20 [doi]
LID - e01650-20
AB  - Omadacycline is a once-daily oral or intravenous (i.v.) aminomethylcycline 
      antibiotic approved in the United States for the treatment of community-acquired 
      bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections 
      (ABSSSI) in adults. Omadacycline pharmacokinetics were characterized in 18 
      patients with hepatic impairment and 12 matched healthy subjects. Patients with 
      hepatic impairment received i.v. omadacycline at 100 mg (mild hepatic impairment) 
      or 50 mg (moderate and severe hepatic impairment) and oral omadacycline at 300 mg 
      (mild hepatic impairment) or 150 mg (moderate hepatic impairment); oral 
      omadacycline was not evaluated in those with severe hepatic impairment. Safety 
      monitoring included the collection of adverse events (AEs), performance of 
      laboratory tests, determination of vital signs, and performance of 
      electrocardiograms. Omadacycline exposures were similar in patients with hepatic 
      impairment and healthy subjects following i.v. or oral administration, with the 
      geometric mean ratios for the area under the concentration-time curve and the 
      maximum drug concentration ranging from 0.79 to 1.42. Omadacycline was safe and 
      well tolerated. Overall, 13/30 (43.3%) participants experienced an AE; those 
      occurring in more than 1 participant included headache (13.3%), nausea (6.7%), 
      infusion-site pain (6.7%), contusion (6.7%), and dizziness (6.7%), with no 
      differences based on the degree of hepatic impairment or the route of 
      administration. Asymptomatic increases in heart rate were observed; none was 
      considered an AE. These findings suggest that no omadacycline dose adjustment is 
      warranted in patients with hepatic impairment.
CI  - Copyright (c) 2020 Kovacs et al.
FAU - Kovacs, Steven J
AU  - Kovacs SJ
AD  - Novartis Institute for BioMedical Research, Novartis Pharmaceuticals, East 
      Hanover, New Jersey, USA.
FAU - Ting, Lillian
AU  - Ting L
AD  - Novartis Institute for BioMedical Research, Novartis Pharmaceuticals, East 
      Hanover, New Jersey, USA.
FAU - Praestgaard, Jens
AU  - Praestgaard J
AD  - Novartis Institute for BioMedical Research, Novartis Pharmaceuticals, East 
      Hanover, New Jersey, USA.
FAU - Sunkara, Gangadhar
AU  - Sunkara G
AD  - Novartis Institute for BioMedical Research, Novartis Pharmaceuticals, East 
      Hanover, New Jersey, USA.
FAU - Sun, Haiying
AU  - Sun H
AD  - Novartis Institute for BioMedical Research, Novartis Pharmaceuticals, East 
      Hanover, New Jersey, USA.
FAU - Stein, Daniel S
AU  - Stein DS
AD  - Novartis Institute for BioMedical Research, Novartis Pharmaceuticals, East 
      Hanover, New Jersey, USA.
FAU - Tanaka, S Ken
AU  - Tanaka SK
AD  - Paratek Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USA 
      ken.tanaka@paratekpharma.com.
FAU - Villano, Stephen
AU  - Villano S
AD  - Paratek Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201020
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Tetracyclines)
RN  - 090IP5RV8F (omadacycline)
SB  - IM
EIN - Antimicrob Agents Chemother. 2020 Dec 16;65(1):. PMID: 33328319
MH  - Administration, Intravenous
MH  - Administration, Oral
MH  - Adult
MH  - Area Under Curve
MH  - *Community-Acquired Infections/drug therapy
MH  - Humans
MH  - *Liver Diseases/drug therapy
MH  - Tetracyclines/adverse effects
PMC - PMC7577144
OTO - NOTNLM
OT  - aminomethylcycline
OT  - hepatic impairment
OT  - omadacycline
OT  - pharmacokinetics
EDAT- 2020/08/26 06:00
MHDA- 2021/06/22 06:00
PMCR- 2020/10/20
CRDT- 2020/08/26 06:00
PHST- 2020/07/29 00:00 [received]
PHST- 2020/07/31 00:00 [accepted]
PHST- 2020/08/26 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/08/26 06:00 [entrez]
PHST- 2020/10/20 00:00 [pmc-release]
AID - AAC.01650-20 [pii]
AID - 01650-20 [pii]
AID - 10.1128/AAC.01650-20 [doi]
PST - epublish
SO  - Antimicrob Agents Chemother. 2020 Oct 20;64(11):e01650-20. doi: 
      10.1128/AAC.01650-20. Print 2020 Oct 20.