Abstract
The removal of imipenem and cilastatin by hemodialysis was studied in 14 (for imipenem) and 6 (for cilastatin) subjects. Following intravenous infusion of imipenem and cilastatin at a combined concentration of 10 mg/kg of body weight, drug levels in plasma were determined serially during off- and on-hemodialysis periods, which were 2 and 4 h, respectively. The biexponential decay of the drug levels in plasma was evident in each subject for both imipenem and cilastatin. Hemodialysis accelerated the elimination of both imipenem and cilastatin: the mean elimination-phase half-life of imipenem was shortened from 200 to 78 min, and that of cilastatin was shortened from 445 to 115 min. Hemodialysis clearance of imipenem and cilastatin was calculated by five different methods, each with intrinsic assumptions. The mean hemodialysis clearance of imipenem was estimated to be 74.08 +/- 13.29 ml/min, and that of cilastatin was estimated to be 65.0 +/- 8.6 ml/min, after consideration of various methodological limitations. It was estimated that in a hypothetical anephric patient weighing 60 kg, a 4-h hemodialysis treatment would remove 54.8% of the imipenem and 62.9% of the cilastatin present in the body at the start of dialysis.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Berman S. J., Sugihara J. G., Nakamura J. M., Kawahara K. K., Wong E. G., Musgrave J. E., Wong L. M., Siemsen A. M. Multiple-dose study of imipenem/cilastatin in patients with end-stage renal disease undergoing long-term hemodialysis. Am J Med. 1985 Jun 7;78(6A):113–116. doi: 10.1016/0002-9343(85)90112-3. [DOI] [PubMed] [Google Scholar]
- Clissold S. P., Todd P. A., Campoli-Richards D. M. Imipenem/cilastatin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1987 Mar;33(3):183–241. doi: 10.2165/00003495-198733030-00001. [DOI] [PubMed] [Google Scholar]
- Drusano G. L. An overview of the pharmacology of imipenem/cilastatin. J Antimicrob Chemother. 1986 Dec;18 (Suppl E):79–92. doi: 10.1093/jac/18.supplement_e.79. [DOI] [PubMed] [Google Scholar]
- Gibson T. P., Demetriades J. L., Bland J. A. Imipenem/cilastatin: pharmacokinetic profile in renal insufficiency. Am J Med. 1985 Jun 7;78(6A):54–61. doi: 10.1016/0002-9343(85)90102-0. [DOI] [PubMed] [Google Scholar]
- Lee C. S., Marbury T. C. Drug therapy in patients undergoing haemodialysis. Clinical pharmacokinetic considerations. Clin Pharmacokinet. 1984 Jan-Feb;9(1):42–66. doi: 10.2165/00003088-198409010-00003. [DOI] [PubMed] [Google Scholar]
- Lee C. S. The assessment of fractional drug removal by extracorporeal dialysis. Biopharm Drug Dispos. 1982 Apr-Jun;3(2):165–173. doi: 10.1002/bdd.2510030207. [DOI] [PubMed] [Google Scholar]
- Peoples R. W., Cole J. J., Vizzo J. E., Leith W. C., Blagg C. R. Photoelectric measurement of blood flow during hemodialysis. Kidney Int. 1973 Mar;3(3):190–192. doi: 10.1038/ki.1973.28. [DOI] [PubMed] [Google Scholar]
- Takki S., Gambertoglio J. G., Honda D. H., Tozer T. N. Pharmacokinetic evaluation of hemodialysis in acute drug overdose. J Pharmacokinet Biopharm. 1978 Oct;6(5):427–442. doi: 10.1007/BF01062724. [DOI] [PubMed] [Google Scholar]
- Verpooten G. A., Verbist L., Buntinx A. P., Entwistle L. A., Jones K. H., De Broe M. E. The pharmacokinetics of imipenem (thienamycin-formamidine) and the renal dehydropeptidase inhibitor cilastatin sodium in normal subjects and patients with renal failure. Br J Clin Pharmacol. 1984 Aug;18(2):183–193. doi: 10.1111/j.1365-2125.1984.tb02451.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamaoka K., Nakagawa T., Uno T. Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm. 1978 Apr;6(2):165–175. doi: 10.1007/BF01117450. [DOI] [PubMed] [Google Scholar]
