Multiple intravenous dose pharmacokinetic study of carumonam in healthy subjects

J Antimicrob Chemother. 1989 Jan;23(1):107-11. doi: 10.1093/jac/23.1.107.

Abstract

Steady-state pharmacokinetics of carumonam were investigated in twelve healthy adult male volunteers after 20 min intravenous infusions of three consecutive carumonam dosage regimens: 1 g every 8 h (3 g/day) from 0-72 h, 2 g every 8 h (6 g/day) from 88-120 h and 2 g every 6 h (8 g/day) from 132-216 h. Serial plasma samples were collected after the first dose of the first regimen and the last dose of all three regimens and were analysed for carumonam by a specific HPLC method. The overall mean maximal plasma concentrations were 108 and 211 mg/l at the end of infusion of 1 and 2 g, respectively. The steady-state pharmacokinetic parameters and plasma concentration-time profiles of carumonam when adjusted for dose were similar for the three regimens. The overall terminal elimination half-life was 1.4 h (range 1.1-1.8 h), the apparent volume of distribution at steady state reached 11.5 l (range 8.7-15.5 l) and the total systemic clearance amounted to 118 ml/min (range 83-158 ml/min). Considering the frequency of dosing relative to the elimination half-life, accumulation of the drug in plasma was not expected and none was found from any of the three regimens. Carumonam was well tolerated up to 8 g/day and exhibited dose-independent pharmacokinetics which were not altered upon multiple dosing.

MeSH terms

  • Adult
  • Aztreonam / administration & dosage
  • Aztreonam / analogs & derivatives*
  • Aztreonam / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Half-Life
  • Humans
  • Infusions, Intravenous
  • Male

Substances

  • carumonam
  • Aztreonam