Penicillin renal elimination

The dose of aciclovir in patients with renal impairment should be reduced as aciclovir is eliminated by the renal system. Most penicillins are eliminated by the renal system and hence dose reduction of amoxicillin is required in cases of renal impairment. Non-steroidal anti-inflammatory drugs cause the inhibition of the biosynthesis of prostaglandins involved in the maintenance of renal blood flow. This may precipitate acute renal insufficiency in patients with renal impairment. Furthermore non-steroidal anti-inflammatory drugs tend to cause water and sodium retention and hence aggrevate renal impairment. 

The absorption and excretion of carbenicillin in man has been reported [396]. The antibiotic is not absorbed intact from the gut intramuscular injection (which is painful) often provides adequate serum levels (approximately 20 Mg/ntl) but infections with Pseudomonas strains having minimum inhibitory concentrations up to, or higher than, 100 Mg/ml require intravenous thbrapy to achieve such levels. No evidence of active metabolite formation has been obtained. Marked reductions in the half-life (and serum levels) of carbenicillin follow extracorporeal dialysis or peritoneal dialysis, the former producing the most striking effect [397]. These results were, of course, obtained in patients with severe renal failure. Patients with normal renal function rapidly eliminate the drug but, as with all penicillins, renal tubular secretion can be retarded by concurrent administration of probenecid. 

Penicillin G undergoes rapid renal elimination mainly in unchanged form (plasma ti/2 - 0.5 h). The duration of the effect can be prolonged by ... 

Combination with probenecid. Renal elimination of penicillin occurs chiefly via the anion (acid)-secretory system of the proximal tubule (-COOH of 6-APA). The acid probenecid (p. 316) competes for this route and thus retards penicillin eUmination ... 

Some penicillins cannot be given orally as their beta-lactam ring is hydrolyzed and inactivated in the stomach by gastric acid. In general intramuscular injections are painful and therefore not advised. The pharmacokinetic behavior of penicillins is further characterized by short elimination half-lives. Renal elimination is prominent. 

Renal elimination of foreign compounds may change dramatically with increasing age by factors such as reduced renal blood flow, reduced glomerular filtration rate, reduced tubular secretory activity, and a reduction in the number of functional nephrons. It has been estimated that in humans, beginning at age 20 years, renal function declines by about 10% for each decade of life. This decline in renal excretion is particularly important for drugs such as penicillin and digoxin, which are eliminated primarily by the kidney. 

Penicillin G is excreted by the kidneys, with 90% of renal elimination occurring via tubular secretion and 10% by glomerular filtration. Probenecid blocks tubular secretion and has been used to increase the serum concentration and prolong the half-life of penicillin G and other penicillins. Additional pharmacokinetic information can be found in Table 45.1. 

The antipseudomonal penicillins undergo renal elimination (Table 45.1). Piperacillin and ticarcillin have minimal hepatic metabolism. In contrast, mezlocillin has significant hepatic metabolism and requires dose adjustment in patients with hepatic insufficiency. 

METHOTREXATE PENICILLINS t plasma concentrations of methotrexate and risk of toxic effects of methotrexate, e.g. myelosuppression, liver cirrhosis, pulmonary toxicity Penicillins 1 renal elimination of methotrexate by renal tubular secretion, which is the main route of elimination of methotrexate. Penicillins compete with methotrexate for renal elimination. Displacement from proteinbinding sites may occur and is only a minor contribution to the interaction Avoid concurrent use. If concurrent use is necessary, monitor clinically and biochemically for blood dyscrasia, liver toxicity and pulmonary toxicity. Do FBCs and LFTs prior to concurrent treatment... 

From the above account, it is evident that the therapeutic range of the original penicillin G has been considerably extended through the new semi-synthetic products. These are, however, more costly, and should not be prescribed without good reason. An economy can be effected, when giving a member of the amoxycillin family orally, by prescribing oral probenecid 3.16) as well, because this decreases renal elimination of penicillins. 

Excretion - Penicillins are excreted largely unchanged in the urine by glomerular filtration and active tubular secretion. Nonrenal elimination includes hepatic inactivation and excretion in bile this is only a minor route for all penicillins except nafcillin and oxacillin. Excretion by renal tubular secretion can be delayed by coadministration of probenecid. Elimination half-life of most penicillins is short (no... 

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. 

Distribution of penicillin antibiotics is limited to extracellular fluids, but inflammation may enhance their distribution into tissues. Penicillins are actively transported in kidney, brain, and liver. Most penicillins undergo minimal hepatic metabolism and are cleared from the plasma primarily by renal excretion. Secretion of penicillins by the renal tubules results in high urine concentrations and rapid elimination from the body (50). 

Renal failure will result in a diminished elimination of drugs that are primarily secreted, such as penicillins and aminoglycosides, and therefore in a longer half-life of the drug (45). Likewise, liver disease may result in a capacity-limited biotransformation, and consequently in a slower elimination of the drug. Bacterial pneumonia in calves may also result in increased serum oxytetracycline concentrations, a condition that can cause prolonged elimination (46). 

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 ... 

Inhibition of transport processes that carry substances across cells, e.g. blockade of anion transport in the renal tubule cell by probenecid can be used to delay excretion of penicillin, and to enhance elimination of mate... 

Elimination. Renal plasma flow almost doubles and there is more rapid loss of drugs that are excreted by the kidney, e.g. amoxycillin, the dose of which should be doubled for systemic infections (but not for urinary tract infections as penicillins are highly concentrated in the urine). 

These are adapted from the ampicillin molecule, with a side-chain derived from urea. Their major advantages over the carboxypenicillins are higher efficacy against Pseudomonas aeruginosa and the fact that as monosodium salts they deliver on average about 2 mmol of sodium per gram of antimicrobial (see above) and are thus safer where sodium overload should particularly be avoided. They are degraded by many p-lactamases. Ureidopenicillins must be administered parenterally and are eliminated mainly in the urine. Accumulation in patients with poor renal function is less than with other penicillins as 25% is excreted in the bile. An unusual feature of their kinetics is that, as the dose is increased, the plasma concentration rises disproportionately, i.e. they exhibit saturation (zero-order) kinetics. 

Age-related alteration of renal function is a very important factor in selecting the dose regimen. Renal function in newborns is incompletely developed. Neonatal renal plasma flow and glomerular filtration rates (normalized for body surface) are only 30-40% of those of adults. The half-life of penicillin G is 3.2 h in newborns (up to 6 days of age) and 1.4 h in infants (14 days of age or older), whereas in older children and adults, it is about 0.5 h. The mean half-life of gentamicin is about 5h in newborns under 1 week of age and about 3 h in infants 1-4 weeks of age. The half-life of gentamicin in older infants and adults is approximately 2 h. Thus, drugs that depend on renal excretion as the principal mode of elimination would be expected to have a longer residence time in infants. 

Uncharged hydrophilic substances prefer glomerular filtration for their renal handling/elimination in contrast to the many ionized organic substances handled by additional nephron mechanisms, such as tubular secretion (e.g. penicillin). 

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