Linked Life Data

6593092

Source:http://linkedlifedata.com/resource/pubmed/id/6593092

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pubmed-article:6593092pubmed:abstractTextThe antibiotic imipenum (thienamycin-formamidine) is partially hydrolyzed during excretion by a renal brush border dehydropeptidase. The co-administration of imipenum with the renal dehydropeptidase inhibitor cilastatin results in an increase of the urinary recovery of the antibiotic, both in animals and humans. To study the pharmacokinetics of imipenem and cilastatin, subjects with normal renal function and patients with different degrees of renal insufficiency received intravenously 250 mg imipenum alone and 250 mg imipenem with 250 mg cilastatin. The mean plasma half-life of imipenem varied from 52 min in subjects with normal renal function to 173 min in subjects with end-stage renal failure studied while off-dialysis. The plasma half-life of imipenem was not affected by the co-administration of cilastatin. The mean plasma half-life of cilastatin varied from 54 min in normals to 798 min in patients with end-stage renal failure. The co-administration of cilastatin resulted in an increase of the urinary concentration and in the urinary recovery of imipenem, the effect being more pronounced in the subjects with normal or only mildly impaired renal function. The plasma clearance of imipenem was decreased when cilastatin was co-administered, possibly due to inhibition of tubular secretion of imipenem. Elimination studies performed during haemodialysis indicated efficient removal of both imipenem and cilastatin during a 4 h session. In view of the important increase in half-life of cilastatin as a function of increasing renal failure, a dosage reduction is proposed in patients with severe renal failure. It is recommended that the maximum dose of imipenem/cilastatin would be limited to either 1000/1000 mg twice daily or 500/500 mg four times daily in patients with a creatinine clearance of less than 15 ml/min. Also, a supplementary dose of imipenem and cilastatin after dialysis is recommended.lld:pubmed
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pubmed-article:6593092pubmed:articleTitleThe pharmacokinetics of imipenem (thienamycin-formamidine) and the renal dehydropeptidase inhibitor cilastatin sodium in normal subjects and patients with renal failure.lld:pubmed
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