Pharmacokinetics and unexpected safety issues of LBM415, a novel oral peptide deformylase inhibitor

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dc.contributor.authorRolan, P.
dc.contributor.authorSun, H.
dc.contributor.authorMacLeod, C.
dc.contributor.authorBracken, K.
dc.contributor.authorEvans, T.
dc.date.issued2011
dc.description.abstractPeptide 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.
dc.description.statementofresponsibilityP Rolan, H Sun, C MacLeod, K Bracken, and TG Evans
dc.identifier.citationClinical Pharmacology and Therapeutics, 2011; 90(2):256-262
dc.identifier.doi10.1038/clpt.2011.101
dc.identifier.issn0009-9236
dc.identifier.issn1532-6535
dc.identifier.urihttp://hdl.handle.net/2440/67494
dc.language.isoen
dc.publisherMosby Inc
dc.rights© 2011 American Society for Clinical Pharmacology and Therapeutics
dc.source.urihttps://doi.org/10.1038/clpt.2011.101
dc.subjectHumans
dc.subjectMethemoglobinemia
dc.subjectCyanosis
dc.subjectOxygen
dc.subjectAmidohydrolases
dc.subjectPeptides
dc.subjectEnzyme Inhibitors
dc.subjectFasting
dc.subjectArea Under Curve
dc.subjectDouble-Blind Method
dc.subjectEating
dc.subjectDose-Response Relationship, Drug
dc.subjectHalf-Life
dc.subjectAdult
dc.subjectMale
dc.titlePharmacokinetics and unexpected safety issues of LBM415, a novel oral peptide deformylase inhibitor
dc.typeJournal article
pubs.publication-statusPublished

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