Pharmacokinetics of carumonam after single and multiple 1- and 2-g dosage regimens

The pharmacokinetics of carumonam after single and multiple intravenous administration of 1- and 2-g dosage regimens were studied in 12 young male volunteers. Plasma and urine samples were collected in serial order for 24 h and assayed by high-pressure liquid chromatography. The mean elimination half-life of carumonam was not significantly affected by either dosage regimen or single dose versus steady state, ranging from 1.3 to 1.5 h. Mean concentrations at the end of the interval were not influenced by a multiple-dose administration. The normalized volume of distribution was independent of the dose, with values ranging from 0.16 to 0.19 liters/kg. After multiple administration, carumonam was cleared from the body more rapidly: from 96.2 to 121.7 ml/min after 1 g every 8 h, and from 102.1 to 122.3 ml/min after 2 g every 8 h (P less than 0.05). After 24 h, 75.0 to 80.7% of the dose was excreted unchanged in the urine. The protein binding of carumonam to human plasma remained stable at 28%. Carumonam was well tolerated by the volunteers.