Pharmacokinetics of carumonam in patients with renal insufficiency.
The pharmacokinetics of carumonam after a single 1,000-mg intravenous infusion (20 min) were evaluated in four groups of subjects who had various degrees of renal impairment: group 1, CLCR greater than 60 ml/min; group 2, CLCR = 30 to 60 ml/min; group 3, CLCR = 10 to 30 ml/min; and group 4, CLCR less than 10 ml/min). The elimination half-life of carumonam increased with decreasing creatinine clearance (CLCR) from 1.7 h in group 1 to 11.3 h in group 4. Peak carumonam concentration (103 micrograms/ml) and steady-state volume of distribution (12.8 liters) did not change with decreasing CLCR. Total body clearance (r = 0.98), renal clearance (r = 0.98), and nonrenal clearance (r = 0.67) of carumonam correlated with decreasing CLCR. Mean nonrenal clearance was 21 ml/min in group 1 and 12 ml/min in group 4. With regard to dosage, patients with a CLCR above 60 ml/min should receive their standard maintenance dose of carumonam without any changes; patients with a CLCR between 30 and 60 ml/min should receive the dose every 12 h; and individuals with a CLCR between 10 and 30 ml/min should be given the dose once a day. Patients with a CLCR of less than 10 ml/min should receive one-half of the dose once a day. Our recommended dosage regimens should produce within the CLCR borderlines of each group average plasma concentrations that are between one and two times that achieved in normal subjects with a t.i.d. dosage regimen.
D000328:Adult; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001398:Aztreonam / Q000031:analogs & derivatives*; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D007700:Kinetics; D007769:Lactams; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged
D000900:Anti-Bacterial Agents; D007769:Lactams; C044145:carumonam; D003404:Creatinine; D001398:Aztreonam