Imipenem/cilastatin: pharmacokinetic profile in renal insufficiency.
The pharmacokinetics of 250 mg each of intravenous imipenem and cilastatin in combination and 250 mg of cilastatin alone were studied in subjects with varying degrees of renal clearance. Renal disease did not change the volume of distribution of either drug. When the glomerular filtration rate was greater than 100 ml per minute, 48.6 percent of imipenem and 57.1 percent of cilastatin were recovered unchanged in the urine. Consequently, as the glomerular filtration rate declined, the half-life of imipenem increased from 1.02 hours in normal subjects to 3.69 hours in those undergoing dialysis. For cilastatin, the comparable values were 0.86 and 17.08 hours, respectively. The kinetics of cilastatin were unaffected by imipenem. The greater effect of renal disease on the half-life of cilastatin was due to a concomitant 87 percent reduction in nonrenal clearance. Both drugs were removed by hemodialysis. Dialysis reduced the half-life of imipenem from 4.80 to 2.45 hours and that of cilastatin from 16.63 to 3.86 hours. Therefore, dose adjustments will be required in patients with markedly reduced renal function and supplemental dosing will be required after hemodialysis.[1]References
- Imipenem/cilastatin: pharmacokinetic profile in renal insufficiency. Gibson, T.P., Demetriades, J.L., Bland, J.A. Am. J. Med. (1985) [Pubmed]
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