Pharmacokinetics and safety of NM441, a new quinolone, in healthy male volunteers

J Clin Pharmacol. 1994 Sep;34(9):930-7. doi: 10.1002/j.1552-4604.1994.tb04007.x.

Abstract

The safety and pharmacokinetics of NM441, a prodrug of a new thiazeto-quinoline carboxylic acid derivative, NM394, were evaluated in healthy male volunteers given the drug orally in single doses of 20, 50, 100, 200, and 400 mg, and multiple doses of 300 mg twice daily for 6.5 days. No remarkable abnormalities were observed in symptoms, physical tests, laboratory tests, electrocardiogram (ECG), electroencephalogram (EEG), or equilibrium test. The mean plasma concentrations of active metabolite NM394 peaked between 0.5 and 1.0 hours, and the maximum concentrations were 0.68, 1.09, and 1.88 micrograms/mL at doses of 100, 200, and 400 mg, respectively. The mean half-lives were 7.7 to 8.9 hours and were not affected by dose. The mean urinary excretion rates of NM394 were 46.0, 38.3, and 30.6% of the doses within 48 hours, respectively, and other metabolites were excreted in urine by 7% of the doses. The mean salivary concentrations of NM394 were approximately 20% of the plasma concentrations. The mean fecal excretion rates of NM394 and NM441 were 52.9 and 4.2%, respectively within 72 hours after dosing of 400 mg. The Cmax, AUC, and urinary excretion rates were not altered by food intake, whereas the Tmax was prolonged slightly. In the multiple-dose study, the steady state of plasma concentration of NM394 was achieved on day 3 or 4, and further accumulation did not occur thereafter. The mean urinary excretion rate of NM394 was 49.0% during and 48 hours after the multiple administration. The acceptable safety and tolerance and defined pharmacokinetic characteristics of NM441 support further testing.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / adverse effects
  • Anti-Infective Agents / pharmacokinetics*
  • Dioxolanes / administration & dosage
  • Dioxolanes / adverse effects
  • Dioxolanes / pharmacokinetics*
  • Drug Administration Schedule
  • Fluoroquinolones*
  • Food
  • Half-Life
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Piperazines / administration & dosage
  • Piperazines / adverse effects
  • Piperazines / pharmacokinetics*
  • Prodrugs / administration & dosage
  • Prodrugs / adverse effects
  • Prodrugs / pharmacokinetics*
  • Quinolones / administration & dosage
  • Quinolones / adverse effects
  • Quinolones / pharmacokinetics*

Substances

  • Anti-Infective Agents
  • Dioxolanes
  • Fluoroquinolones
  • Piperazines
  • Prodrugs
  • Quinolones
  • prulifloxacin