Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/67494
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Pharmacokinetics and unexpected safety issues of LBM415, a novel oral peptide deformylase inhibitor |
Author: | Rolan, P. Sun, H. MacLeod, C. Bracken, K. Evans, T. |
Citation: | Clinical Pharmacology and Therapeutics, 2011; 90(2):256-262 |
Publisher: | Mosby Inc |
Issue Date: | 2011 |
ISSN: | 0009-9236 1532-6535 |
Statement of Responsibility: | P Rolan, H Sun, C MacLeod, K Bracken, and TG Evans |
Abstract: | Peptide deformylase (PDF) inhibitors represent a potential new class of antibiotics targeting a large number of bacterial species. We studied the pharmacokinetics and safety of LBM415, a novel PDF inhibitor, administered as a single oral dose at 100-3,000 mg in the fasted state and at 1,000 mg in the fed state in healthy volunteers. LBM415 was then administered at dosages ranging from 100 mg q.d. to 1,000 mg t.i.d. for 11 days. Dose-proportional pharmacokinetics was observed, with a peak plasma concentration (C(max)) of 17.85 ± 5.96 µg/ml at 1,000 mg b.i.d. (the projected therapeutic dose) and an area under the concentration-time curve (AUC)(0-24h) of 36.83 ± 10.36 µg/ml·h. The half-life, as determined after a 1,000-mg single dose, was 2.18 ± 0.61 h. The compound was well tolerated at low doses, but at the highest dose, 1,000 mg t.i.d., reversible cyanosis and low oxygen saturation, attributable to methemoglobinemia, were detected on day 11. Oxygen saturation was as low as 88% in one subject on day 11. |
Keywords: | Humans Methemoglobinemia Cyanosis Oxygen Amidohydrolases Peptides Enzyme Inhibitors Fasting Area Under Curve Double-Blind Method Eating Dose-Response Relationship, Drug Half-Life Adult Male |
Rights: | © 2011 American Society for Clinical Pharmacology and Therapeutics |
DOI: | 10.1038/clpt.2011.101 |
Published version: | http://dx.doi.org/10.1038/clpt.2011.101 |
Appears in Collections: | Aurora harvest 5 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.