Carbapenems pharmacokinetics

Mechanism of Action A fixed-combination carbapenem. Imipenem penetrates the bacterial cell membrane and binds to penicillin-binding proteins, inhibiting cell wall synthesis. Cilastatin competitively inhibits the enzyme dehydropeptidase, preventing renal metabolism of imipenem. Therapeutic Effect Produces bacterial cell death. Pharmacokinetics Readily absorbed after IM administration. Protein binding 13%-21%. Widely distributed. Metabolized in the kidneys. Primarilyexcreted in urine. Removed by hemodialysis. Half-life 1 hr (increased in impaired renal function). 

The use of piperacillin is reported to be a risk factor for aminoglycoside-associated nephrotoxicity. A reduction in serum aminoglycoside levels can occur if aminoglycosides and penicillins are given together to patients with severe renal impairment. No pharmacokinetic interaction of importance appears to occur with intravenous aminoglycoside and penicillins in those with normal renal function or between aminoglycosides and carbapenems. The serum levels of oral phenoxymethylpenicillin can be halved by oral neomycin. 

Carbapenems An old Chinese man with epilepsy had seizures when meropenem was added to treatment with valproate [407 ]. In a retrospective study of six critically ill patients taking valproate who concurrently received meropenem (n = 4), imipenem (n = 1), or ertapenem (n = 1) mean plasma valproate trough concentrations fell by 58% and estimated mean valproate clearance increased by 191% compared with values obtained while they were not receiving a carbapenem five patients had generalized seizures during concurrent valproate -b carbapenem treatment, including two with no prior history of seizures [408 ]. Meropenem is an enzyme inducer. Because of this pharmacokinetic interaction, concurrent use of these medications should be avoided. 

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