Development of an Adult Physiologically Based Pharmacokinetic Model of Solithromycin in Plasma and Epithelial Lining Fluid.

Journal Article (Journal Article)

Solithromycin is a fluoroketolide antibiotic under investigation for community-acquired bacterial pneumonia (CABP). We developed a whole-body physiologically based pharmacokinetic (PBPK) model for solithromycin in adults using PK-Sim and MoBi version 6.2, which incorporated time-dependent CYP3A4 auto-inhibition. The model was developed and evaluated using plasma and epithelial lining fluid (ELF) concentration data from 100 healthy subjects and 22 patients with CABP (1,966 plasma, 30 ELF samples). We performed population simulations and calculated the number of observations falling outside the 90% prediction interval. For the oral regimen (800 mg on day 1 and 400 mg daily on days 2-5) that was evaluated in phase III studies, 11% and 23% of observations from healthy adults fell outside the 90% prediction interval for plasma and ELF, respectively. This regimen should be effective because ≥97% of simulated adults achieved area under the concentration vs. time curve (AUC) to minimum inhibitory concentration ratios associated with a log10 colony forming unit reduction in ELF.

Full Text

Duke Authors

Cited Authors

  • Salerno, SN; Edginton, A; Cohen-Wolkowiez, M; Hornik, CP; Watt, KM; Jamieson, BD; Gonzalez, D

Published Date

  • December 2017

Published In

Volume / Issue

  • 6 / 12

Start / End Page

  • 814 - 822

PubMed ID

  • 29068158

Pubmed Central ID

  • PMC5744174

Electronic International Standard Serial Number (EISSN)

  • 2163-8306

Digital Object Identifier (DOI)

  • 10.1002/psp4.12252


  • eng

Conference Location

  • United States