Abstract
Imipenem renal clearance was studied in six children (three males, three females; 2.9–11.2 years of age) following a single intravenous dose (21.7±5.1 mg/kg) of imipenem/cilastatin (1∶1). In an approximately six-hour period following drug administration, 65.3±9.7% of the imipenem dose was excreted in the urine unchanged. The renal clearance (280.03±24.34 ml/min/1.73 m2) of imipenem was found to account for 69.2% of the corresponding plasma imipenem clearance (404.89±24.83 ml/min/1.73 m2). Contrary to existing adult data, the imipenem renal clearance in our subjects was 1.95-fold greater than the estimated creatinine clearance, suggesting significant tubular secretion of imipenem in children. Examination of urinary imipenem excretion rate versus plasma concentration relationships in three of the children revealed a potential renal tubular reabsorption component for imipenem in children. Comparison of renal imipenem clearance data in these children to similar data from adults suggests that quantitatively important developmental differences may exist for the renal handling of imipenem.
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Hanslo, D., King, A., Shannon, K., Warren, C., Phillips, I.: N-formimidoyl thienamycin (MK0787):in vitro antibacterial activity and susceptibility to beta-lactamases compared with that of cefotaxime, moxalactam, and other beta-lactam antibiotics. Journal of Antimicrobial Chemotherapy 1981, 7: 607–617.
Neu, H. C., Labthavikal, P.: Comparativein vitro activity of N-formimidoyl thienamycin against grampositive and gram-negative aerobic and anaerobic species and itsβ-lactamase stability. Antimicrobial Agents and Chemotherapy 1982, 21: 180–187.
Kropp, H., Sundelof, J. G., Hajdn, R., Kahan, F. M.: Metabolism of thienamycin and related carbapenem antibiotics by the renal dipeptidase, dehydropeptidase-1. Antimicrobial Agents and Chemotherapy 1982, 22: 62–70.
Norrby, S. R., Alestig, K., Björnegard, B., Burman, L. A., Ferber, F., Huber, J. L., Jones, K. H., Kahan, F. M., Kahan, J. S., Kropp, H., Meisinger, M. S., Sundelof, J. G.: Urinary recovery of N-formimidoyl thienamycin (MK0787) as affected by coadministration of N-formimidoyl thienamycin dehydropeptidase inhibitors. Antimicrobial Agents and Chemotherapy 1983, 23: 300–307.
Norrby, S. R., Alestig, K., Ferber, F., Huber, J. L., Jones, K. H., Kahan, F. M., Meisinger, M. A., Rogers, J. D.: Pharmacokinetics and tolerance of N-formimidoyl thienamycin (MK0787) in humans. Antimicrobial Agents and Chemotherapy 1983, 23: 293–299.
Reed, M. D., Stern, R. C., O'Brien, C. S., Myers, C. M., Blumer, J. L.: Efficacy and pharmacokinetics of imipenem/cilastatin in cystic fibrosis. Clinical Pharmacology and Therapeutics 1984, 35: 268.
Schwartz, G. J., Haycock, G. B., Edelman, C. M., Spitzer, A.: A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976, 58: 259–263.
Brown, R. D., Manno, J. F.: ESTRIP, a BASIC computer program for obtaining initial polyexponential parameter estimates. Journal of Pharmaceutical Sciences 1978, 67: 1786–1791.
Loo, J. K., Riegelman, S. L.: Assessment of pharmacokinetic constants from post-infusion blood curves obtained after intravenous infusion. Journal of Pharmaceutical Sciences 1970, 59: 53–55.
Gibaldi, M., Perrier, D.: One-compartment model. In: Gibaldi, M., Perrier, D. (ed.): Pharmacokinetics. 2nd Edition. Marcel Dekker, Inc., New York, 1982, p. 12.
Rowland, M., Tozer, T. N.: Clearance and renal excretion. In: Rowland, M., Tozer, T. N. (ed.): Clinical Pharmacokinetics: Concepts and Applications. Lea and Febiger, Philadelphia, 1980, p. 55–57.
Batson, H. D. (ed.: An Introduction to Statistics in the Medical Sciences. Burgess Publishing Co., Minneapolis, 1956, p. 55–61.
Dixon, W. J., Massey, F. J. (ed.: Introduction to Statistical Analysis. 3rd Edition. McGraw Hill Publishing Co., New York, 1956, p. 193–221.
Snedecor, G. W., Cochran, W. G. (ed.: Statistical Methods. 6th Edition. Iowa State University Press, Ames, 1967, p. 381–418.
Morselli, P. L., Franco-Morselli, R., Bossi, L.: Clinical pharmacokinetics in newborns and infants: age-related differences and therapeutic implications. Clinical Pharmacokinetics 1980, 5: 485–527.
Soyka, L. F.: Pediatric clinical pharmacology of digoxin. Pediatric Clinics of North America 1981, 28: 203–216.
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Jacobs, R.F., Kearns, G.L., Brown, A.L. et al. Renal clearance of imipenem in children. Eur. J. Clin. Microbiol. 3, 471–474 (1984). https://doi.org/10.1007/BF02017378
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DOI: https://doi.org/10.1007/BF02017378