Penicillin glomerular filtration

Excretion via the kidney can be a straightforward question of glomerular filtration, followed by passage down the kidney tubules into the bladder. However, there can also be excretion and reabsorption across the tubular wall. This may happen if an ionized form within the tubule is converted into its nonpolar nonionized form because of a change in pH. The nonionized form can then diffuse across the tubular wall into plasma. Additionally, there are active transport systems for the excretion of lipophilic acids and bases across the wall of the proximal tubule. The antibiotic penicillin can be excreted in this way. 

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... 

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. 

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). 

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. 

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 ... 

These resemble the penicillins structurally, in mode of action and in general lack of toxicity. They are primarily excreted by the kidney by tubular secretion and some also by glomerular filtration (e.g. cephalothin) or only by glomerular filtration (e.g. cefazolin). Cefoperazone is excreted by the bile. Cefotaxime undergoes hepatic biotransformation to active metabolites. Hypersensitivity reactions are qualitatively similar to those of the penicillins, but the epileptogenic potential is less. 

Aztreonam - intramuscular or intravenous - is excreted unchanged by glomerular filtration and renal tubular secretion. It lacks the allergenic tricyclic nuclear structure of penicillins, cephalosporins and carbapenem beta-lactams. 

Elimination. Glomerular filtration, tubular secretion and reabsorption are low in the neonate (even lower in preterm babies) only reaching adult values in relation to body surface area at 2-5 months. Therefore drugs that are eliminated by the kidney (e.g. aminoglycosides, penicillins, diuretics) must be given in reduced dose after about 6 months. 

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. 

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). 

Elimination of the penicillins is primarily via the kidneys, by glomerular filtration and active tubular secretion. The half-life is approximately 1 h after i.v. injection. Because of slow absorption from the injection site, the half-life of procaine benzylpenicillin (procaine penicillin) is approximately 7h. 

Drugs that undergo both glomerular filtration and active tubular secretion have a very short half-life. Penicillin is... 

Drugs which are either water-soluble or get metabolized gradually are mostly eliminated through the kidneys by the aid of these three essential phenomena, viz seeretion, glomerular filtration and tubular reabsorption. For instance, probenecid considerably retards tubular seeretion of penicillin thereby enhaneing its duration of action appreciably. 

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