Single-dose pharmacokinetics of Ro 17-2301 (AMA-1080), a monocyclic beta-lactam, in humans.
Ro 17-2301 (AMA-1080) is a new N-sulfonated monocyclic beta-lactam that is highly active against gram-negative bacteria, especially against Enterobacteriaceae and Haemophilus, Neisseria, and Pseudomonas spp. (Kondo et al., Proc. Int. Congr. Chemother. 13th, Vienna, Austria, p. 56/1-56/5, 1983). The single-dose pharmacokinetics of this compound were studied in six healthy male volunteers who received intravenous infusions of 500, 1,000, and 2,000 mg. A good linear correlation (r2 = 0.99) was found between the dose infused and the resulting area under the plasma concentration-time curve. Maximal plasma concentrations of 36, 78, and 150 micrograms/ml appeared after doses of 500, 1,000, and 2,000 mg, respectively. The mean terminal elimination half-life was 1.8 h (range, 1.4 to 2.3 h), the apparent volume of distribution at steady state was 17 liters, and the total systemic clearance was 150 ml/min. Within 72 h 78 to 89% of the dose was recovered intact from urine. After administration of 14C-labeled Ro 17-2301, 96% of the radioactivity was found in the urine and 3% was found in the feces. The concomitant administration of probenecid did not affect the renal clearance or urinary excretion of this beta-lactam, an indication that the renal elimination of this substance is only by glomerular filtration. Ro 17-2301 was 18% bound to human plasma protein, and this binding was independent of concentration between 25 and 400 micrograms/ml. Based on these data, the pharmacokinetics of this monocyclic beta-lactam should be predictable in the foreseen dose ranges.
D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood / Q000378:metabolism* / Q000652:urine; D001398:Aztreonam / Q000031:analogs & derivatives*; D002986:Clinical Trials as Topic; D003956:Dialysis; D005243:Feces / Q000032:analysis; D006207:Half-Life; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism; D007700:Kinetics; D008297:Male; D011339:Probenecid / Q000494:pharmacology; D011485:Protein Binding; D014462:Ultrafiltration; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; C044145:carumonam; D001398:Aztreonam; D011339:Probenecid