Abstract
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.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bolton W. K., Scheld W. M., Spyker D. A., Sande M. A. Pharmacokinetics of cefoperazone in normal volunteers and subjects with renal insufficiency. Antimicrob Agents Chemother. 1981 May;19(5):821–825. doi: 10.1128/aac.19.5.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cockcroft D. W., Gault M. H. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41. doi: 10.1159/000180580. [DOI] [PubMed] [Google Scholar]
- Dettli L. Drug dosage in renal disease. Clin Pharmacokinet. 1976;1(2):126–134. doi: 10.2165/00003088-197601020-00004. [DOI] [PubMed] [Google Scholar]
- Drayer D. E., Lowenthal D. T., Restivo K. M., Schwartz A., Cook C. E., Reidenberg M. M. Steady-state serum levels of quinidine and active metabolites in cardiac patients with varying degrees of renal function. Clin Pharmacol Ther. 1978 Jul;24(1):31–39. doi: 10.1002/cpt197824131. [DOI] [PubMed] [Google Scholar]
- Gibson T. P., Atkinson A. J., Jr, Matusik E., Nelson L. D., Briggs W. A. Kinetics of procainamide and N-acetylprocainamide in renal failure. Kidney Int. 1977 Dec;12(6):422–429. doi: 10.1038/ki.1977.133. [DOI] [PubMed] [Google Scholar]
- Gibson T. P., Granneman G. R., Kallal J. E., Sennello L. T. Cefsulodin kinetics in renal impairment. Clin Pharmacol Ther. 1982 May;31(5):602–608. doi: 10.1038/clpt.1982.84. [DOI] [PubMed] [Google Scholar]
- Imada A., Kondo M., Okonogi K., Yukishige K., Kuno M. In vitro and in vivo antibacterial activities of carumonam (AMA-1080), a new N-sulfonated monocyclic beta-lactam antibiotic. Antimicrob Agents Chemother. 1985 May;27(5):821–827. doi: 10.1128/aac.27.5.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leber H. W., Schütterle G. Oxidative drug metabolism in liver microsomes from uremic rats. Kidney Int. 1972 Sep;2(3):152–158. doi: 10.1038/ki.1972.85. [DOI] [PubMed] [Google Scholar]
- Mezey E., Tobon F. Rates of ethanol clearance and activities of the ethanol-oxidizing enzymes in chronic alcoholic patients. Gastroenterology. 1971 Nov;61(5):707–715. [PubMed] [Google Scholar]
- Reidenberg M. M. The binding of drugs to plasma proteins and the interpretation of measurements of plasma concentrations of drugs in patients with poor renal function. Am J Med. 1977 Apr;62(4):466–470. doi: 10.1016/0002-9343(77)90398-9. [DOI] [PubMed] [Google Scholar]
- Stoeckel K., Koup J. R. Pharmacokinetics of ceftriaxone in patients with renal and liver insufficiency and correlations with a physiologic nonlinear protein binding model. Am J Med. 1984 Oct 19;77(4C):26–32. [PubMed] [Google Scholar]
- Tozer T. N. Concepts basic to pharmacokinetics. Pharmacol Ther. 1981;12(1):109–131. doi: 10.1016/0163-7258(81)90077-2. [DOI] [PubMed] [Google Scholar]
- Tygstrup N. Determination of the hepatic elimination capacity (Lm) of galactose by single injection. Scand J Clin Lab Invest Suppl. 1966;18:118–125. [PubMed] [Google Scholar]
- Verbeeck R., Tjandramaga T. B., Mullie A., Verbesselt R., Verberckmoes R., de Schepper P. J. Biotransformation of diflunisal and renal excretion of its glucuronides in renal insufficiency. Br J Clin Pharmacol. 1979 Mar;7(3):273–282. doi: 10.1111/j.1365-2125.1979.tb00932.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weidekamm E., Stoeckel K., Egger H. J., Ziegler W. H. Single-dose pharmacokinetics of Ro 17-2301 (AMA-1080), a monocyclic beta-lactam, in humans. Antimicrob Agents Chemother. 1984 Dec;26(6):898–902. doi: 10.1128/aac.26.6.898. [DOI] [PMC free article] [PubMed] [Google Scholar]
