Multiple intravenous dose pharmacokinetic study of carumonam in healthy subjects.
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.
Patel
I H
IH
Department of Drug Metabolism, Roche Nutley, Switzerland.
Soni
P P
PP
Portmann
R
R
Suter
K
K
Banken
L
L
Weidekamm
E
E
D000328:Adult; D001398:Aztreonam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male
C044145:carumonam; D001398:Aztreonam