title: Pharmacokinetics and dose recommendations of carumonam in renal failure.
abstract: The pharmacokinetics of (Z)-[[[(2-aminothiazol-4-yl)[[(2S,3S)-2-(hydroxymethyl)-4-oxo-1- sulfoazetidin-3-yl]carbamoyl]methylene]amino]oxo]acetic acid, disodium salt (carumonam, Ro 17-2301) after a 2 g intravenous infusion (20 min) were evaluated in 10 healthy volunteers and 20 patients with various degrees of renal failure. The main results of the kinetic parameters in healthy volunteers (mean + SD) corrected for zero infusion time and 70 kg body weight were: t1/2 alpha, 29 +/- 12 min; t1/2 beta, 108 +/- 27 min; AUCtot, 327 +/- 40 mg h/l; Vdss, 12.2 +/- 1.5 l/70 kg; urinary recovery, 78.7 +/- 8.2%; total clearance 103 +/- 13 ml/min; renal clearance, 85 +/- 13 ml/min. Because of the large variation in the degree of renal insufficiency, calculations of the mean values for the pharmacokinetic parameters in the patient group were not generally justified with the exception of the volume of distribution (Vdss = 14.4 +/- 3.0 l/70 kg). To derive dose recommendations, a regression analysis was performed using values from both the volunteer and patient group for the total area under curve (AUCtot) and glomerular filtration rate (GFR), divided by the mean AUCtot value for the volunteers. This curve can be interpreted as giving the dose reduction factor (DRF) as a function of GFR, where by definition, DRF = 1 for healthy (and young) subjects. Using this method of equivalent areas, no (or only a slight) dose reduction is necessary for patients with GFR values above 40 ml/min.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism*; D001398:Aztreonam / Q000031:analogs & derivatives*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D007700:Kinetics; D007769:Lactams; D008875:Middle Aged
chemical_list: D000900:Anti-Bacterial Agents; D007769:Lactams; C044145:carumonam; D001398:Aztreonam