Pharmacology Imipenem/cilastatin

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1 pharmacology

1.1 mechanism of action
1.2 bioavailability
1.3 distribution
1.4 protein binding
1.5 metabolism
1.6 elimination





pharmacology
mechanism of action

imipenem inhibits bacterial cell-wall synthesis binding penicillin-binding proteins; cilastatin prevents renal metabolism of imipenem.


bioavailability

intramuscular injection:



imipenem: 60–75%
cilastatin: 95–100%

distribution

the drug distributed rapidly , tissues , fluids, including sputum, pleural fluid, peritoneal fluid, interstitial fluid, bile, aqueous humor, reproductive organs, , bone; highest concentrations occur in pleural fluid, interstitial fluid, peritoneal fluid, , reproductive organs; low concentrations occur in csf; crosses placenta, , enters breast milk


protein binding

imipenem: 13–21%
cilastatin, 40%

metabolism

imipenem metabolized in kidney dehydropeptidase 1; activity blocked cilastatin.


elimination

half-life (both drugs): 60 min; prolonged renal impairment. excretion (both drugs): urine (~70% unchanged drug)







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