Renal function impairment penicillins

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). 

Dosages Doses vary depending on the drug used. In general, penicillins should be taken on an empty stomach. Patients with impaired renal function may require dose adjustment. 

Metabolism Metabolism of these drugs by the host is usually insignificant, but some metabolism of penicillin G has been shown to occur in patients with impaired renal function. 

Excretion The primary route of excretion is through the organic acid (tubular) secretory system of the kidney (see p. 224), as well as by glomerular filtration. Patients with impaired renal function must have dosage regimens adjusted. Thus the Xyz of penicillin G can increase from a normal of 1/2 -1 hour to 10 hours in individuals with renal failure. Probenecid inhibits the secretion of penicillins. Nafcillin is primarily eliminated through the biliary route. [Note This is also the preferential route for the acylureido penicillins in cases of renal failure.]... 

Penicillins are rapidly eliminated, particularly by glomerular filtration and renal tubular secretion, With some (e.g, cloxacillin), metabolic transformation occurs, especially in anuric patients, When renal function is impaired, 7-10% of the antibiotic will be inactivated by the liver per hour. Adverse drug reactions are ... 

CSF if the meninges are inflamed. Penicillins are organic acids and their rapid clearance from plasma is due to secretion into renal tubular fluid by the anion transport mechanism in the kidney. Renal clearance therefore greatly exceeds the glomerular filtration rate (127 ml/min). The excretion of penicillin can be usefully delayed by concurrently giving probenecid which competes successfully for the transport mechanism. Dosage of penicillins may should be reduced for patients with severely impaired renal function. 

Aqueous crystalline penicillin G sodium 12-18 million units/24 h IV either continuously or in six equally divided doses 4 Preferred in most patients older than 65 years and in those with impairment of the eighth nerve or renal function... 

The decision of which regimen to use depends on the perceived risk versus benefit. For example, a 2-week course of gentamicin in an elderly patient with renal impairment may be associated with ototoxicity, worsening renal function, or both. Furthermore, the 2-week regimen is not recommended for patients with complications such as extracardiac foci. On the other hand, a 4-week course of penicillin alone generally entails greater expense, especially if the patient remains in the hospital. Monotherapy with once-daily ceftriaxone offers ease of administration, facilitates home health care treatment, and may be cost-effective. ... 

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. 

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