Penicillins renal clearance

Penicillin or cephalosporin therapy The PSP excretion test may be used to determine the effectiveness of probenecid in retarding penicillin excretion and maintaining therapeutic levels. The renal clearance of PSP is reduced to about the normal rate when dosage of probenecid is adequate. 

Penicillin G Prevents bacterial cell wall synthesis by binding to and inhibiting cell wall transpeptidases Rapid bactericidal activity against susceptible bacteria Streptococcal infections, meningococcal infections, neurosyphilis IV administration rapid renal clearance (half-life 30 min, so requires frequent dosing (every 4 h) Toxicity Immediate hypersensitivity, rash, seizures... 

In the case of certain drugs, such as the penicillin class, there are energy-dependent active secretory processes that take place in the proximal tubule cells. These secretory processes selectively facilitate the excretion of certain acids (anions) and bases (cations) from the plasma over and above that provided by glomerular filtration. Therefore, in these cases renal clearance is the sum of glomerular filtration and tubular secretion. 

A number of drugs are known to inhibit the renal secretion of certain other drugs, resulting in decreased clearance of the latter. Examples of drugs decreasing the renal clearance of other drugs include probenecid, salicylates, sulfinpyrazone, phenylbutazone, and thiazide diuretics. As mentioned previously, the inhibition of penicillin secretion by probenecid due to competition between the two for renal tubule carriers is used therapeutically to increase penicillin blood levels. 

Second, certain nucleotide phosphonates (e.g., adefovir and cidofovir) are effective antivirals, but their use in the clinic is limited by renal toxicity. This is believed to be caused by avid uptake at the basolateral membrane of renal proximal tubule cells followed by slow transport into the urine at the apical membrane, a sequence of events that results in intracellular drug accumulation and thus toxicity. As with penicillin, the OAT family of transporters has been implicated in cidofovir uptake. Co-administration of probenecid with cidofovir has been shown to decrease renal clearance of the antiviral and reduce its nephrotoxicity, presumably through com-... 

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. 

Most penicillins have significant renal clearance. Patients who have reduced renal function may accumulate large amounts of penicillin over time. Patients with very high serum levels are more likely to develop more serious toxicity (e.g., neurologic effects) than those with lower levels. 

A renal clearance value greater than the GFR indicates that the drug is actively secreted, but a value less than the GFR does not preclude active secretion because tubular reabsorption takes place in the distal nephron. Competitive inhibition provides the only conclusive evidence that a transport process is carrier-mediated for example, probenecid decreases proximal tubular secretion of penicillin G. 

Renal clearance similar to penicillins, with active tubular secretion blocked by probenecid. Dose modification in renal dysfunction, except cefoperazone and ceftriaxone, which are largely eliminated in the bile. 

Probenecid reduces the hepatic clearance of BSP (B23, B25) as well as inhibiting the renal clearance of penicillin, phenol red, and PAH (M5). Probenecid is also a choleretic (G7) the concentration of both BSP and bilirubin in bile are reduced, but the excretion rate of BSP only is affected (S39). There is an increased reflux of dye from the liver to plasma (G7, S39). The effect of the drug as a choleretic and as an inhibitor of BSP... 

Probenecid and Gout. The story of the discovery of probenecid and its usefulness in the treatment of gout is well known to medicinal chemists. Certain sulfanilamide compounds were observed to decrease the renal clearance of penicillin in a study aimed primarily at increasing the usefulness of penicillin during those days when this antibiotic was difficult and expensive to make. 

Renal clearance similar to penicillins, with active tubular secretion blocked by probenecid... 

Uricosuric inhibitor of renal weak acid secretion and reabsorption in segment of proximal tubule prolongs half-life of penicillin, accelerates clearance of uric acid. Used in gout. Sulfinpyrazole is similar. 

In each case the penicillin competes with the probenecid for excretion by the kidney tubules, although with nafcillin, non-renal clearance may also play a part. 

Penicillin is rapidly excreted by the kidneys small amounts are excreted by other routes. About 10% of renal excretion is by glomerular filtration and 90% by tubular secretion. The normal half-life of penicillin G is approximately 30 minutes in renal failure, it may be as long as 10 hours. Ampicillin and the extended-spectrum penicillins are secreted more slowly than penicillin G and have half-lives of 1 hour. For penicillins that are cleared by the kidney, the dose must be adjusted according to renal function, with approximately one fourth to one third the normal dose being administered if creatinine clearance is 10 mL/min or less (Table 43-1). 

Nafcillin is primarily cleared by biliary excretion. Oxacillin, dicloxacillin, and cloxacillin are eliminated by both the kidney and biliary excretion no dosage adjustment is required for these drugs in renal failure. Because clearance of penicillins is less efficient in the newborn, doses adjusted for weight alone result in higher systemic concentrations for longer periods than in the adult. 

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