Cadazolid, a novel antibiotic with potent activity against Clostridium difficile: safety, tolerability and pharmacokinetics in healthy subjects following single and multiple oral doses

J Antimicrob Chemother. 2014 Mar;69(3):706-14. doi: 10.1093/jac/dkt401. Epub 2013 Oct 8.


Objectives: Current treatment options for Clostridium difficile-associated diarrhoea (CDAD) leave a high unmet medical need for new therapies. Cadazolid is a new antibiotic in development for the treatment of CDAD. The objectives of this study were to evaluate its tolerability and pharmacokinetics following single ascending doses (AC-061-101) and multiple ascending doses (AC-061-102).

Methods: Single and multiple (twice daily for 10 days) oral doses of cadazolid between 30 mg and 3000 mg, or placebo, were tested in a total of 64 healthy male subjects. Safety assessments were conducted at regular intervals. Blood, urine and faeces were sampled, and cadazolid concentrations were measured.

Results: Cadazolid was well tolerated up to 3000 mg given twice daily for 10 days. The most common adverse event was headache, with no observed relationship between dose or treatment duration and adverse events. Plasma concentrations of cadazolid were low. No plasma concentrations >3.3 ng/mL were observed after single doses or >6.9 ng/mL after 10 days of multiple doses. Food increased the mean C(max) from 0.73 to 1.87 ng/mL and mean AUC(0-t) from 3.13 to 15.69 ng ·h/mL after a single 300 mg dose. The increase in systemic exposure to cadazolid across doses was less than dose-proportional. The mean cumulative faecal recovery was 81.0%-93.5%. Urinary recovery of unchanged compound was <0.015%.

Conclusions: Cadazolid was well tolerated and its systemic exposure was low. The majority of compound was recovered unchanged in the faeces, thus resulting in high concentrations at the site of action (colon).

Keywords: clinical pharmacology; colon; diarrhoea; exposure; infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / pharmacokinetics*
  • Blood Chemical Analysis
  • Clostridioides difficile / drug effects
  • Diarrhea / drug therapy
  • Feces / chemistry
  • Healthy Volunteers
  • Humans
  • Male
  • Middle Aged
  • Oxazolidinones / administration & dosage
  • Oxazolidinones / adverse effects*
  • Oxazolidinones / pharmacokinetics*
  • Placebos / administration & dosage
  • Urine / chemistry


  • Anti-Bacterial Agents
  • Oxazolidinones
  • Placebos
  • cadazolid