Penicillin excretion

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. 

The penicillins in general, ate renowned for their lack of toxicity. The most common adverse effect of the use of penicillins is an allergic reaction which can change from a mild rash to fatal anaphylactic shock in rate cases. AH penicillins cross the placenta and ate excreted in maternal milk. However, the relative freedom from toxicity tenders these compounds valuable agents during pregnancy and lactation. 

Penicillins, like most antibiotics, are secondary products whose synthesis is not directly linked to growth. The enzymes that produce secondary products are normally repressed or inhibited under conditions which favour rapid growth. In the early work on penicillin, Penicillium rwtatum was grown as a floating mycelium on about 2 cm depth of liquid medium. The mycelium absorbed nutrients from the medium and penicillin was excreted into the medium. The mycelium and spent medium are readily separated. 

The co-administration of drugs which inhibit the transporters involved in renal tubular secretion can reduce the urinaty excretion of drugs which are substrates of the transporter, leading to elevated plasma concentrations of the drugs. For example, probenecid increases the plasma concentration and the duration of effect of penicillin by inhibiting its renal tubular secretion. It also elevates the plasma concentration of methotrexate by the same mechanism, provoking its toxic effects. 

The natural penicillins also have a fairly narrow spectrum of activity, which means that they are effective against only a few strains of bacteria Newer penicillins have been developed to combat this problem. These penicillins are a result of chemical treatment of a biologic precursor to penicillin. Because of their chemical modifications, they are more slowly excreted... 

In those with gout, the serum uric acid level is usually elevated. Sulfinpyrazone increases the excretion of uric acid by the kidneys, which lowers serum uric acid levels and consequently retards the deposit of urate crystals in the joints. Probenecid (Benemid) works in the same manner and may be given alone or with colchicine as combination therapy when there are frequent, recurrent attacks of gout. Probenecid also has been used to prolong the plasma levels of the penicillins and cephalosporins. 

Whole cells are grown for a variety of reasons. The cells may perform a desired transformation of the substrate, e.g., wastewater treatment the cells themselves may be the desired produce, e.g., yeast production or the cells may produce a desired product, e.g., penicillin. In the later case, the desired product may be excreted, as for the penicillin example, and recovered in relatively simple fashion. If the desired product is retained within the cell walls, it is necessary to lyse (rupture) the cells and recover the product from a complex mixture of cellular proteins. This approach is often needed for therapeutic proteins that are created by recombinant DNA technology. The resulting separation problem is one of the more challenging aspects of biochemical engineering. However, culture of the cells can be quite difficult experimentally and is even more demanding theoretically. 

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. 

Benzylpenicillin is rapidly absoibed and rapidly excreted However, certain sparingly soluble salts of benzylpenicillin (benzathine, benethamine and procaine) slowly release penicillin into the circulation over a period of time, thus giving a continuous high concentration in the blood. Simultaneous administration of benzylpenicillin (see Fortified Proeaine Penieillin, BP) may be given initially. 

Tubular secretion is the transfer of substances from the peritubular capillaries into the renal tubule for excretion in urine. This process is particularly important for the regulation of potassium and hydrogen ions in the body it is also responsible for removal of many organic compounds from the body. These may include metabolic wastes as well as foreign compounds, including drugs such as penicillin. Most substances are secreted by secondary active transport. 

Penicillins and cephalosporins Probenecid, aspirin Blocked excretion of /3-lactams Use if prolonged high concentration of /J-lactam desirable... 

Nuclear magnetic resonance (NMR) spectroscopy of untreated biological fluids has been used successfully in metabolic studies of penicillins. Connor et al. [153] used this method to investigate the metabolism and urinary excretion of ampicillin and amoxycillin in humans and rats. In addition to the metabolites 5.49 and 5.50, they detected a dimer of amoxycillin (5.51) in rat urine. 

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. 

Penicillins form several major metabolites which are excreted in the urine (83,84). These metabolites are usually inactive microbio-logically and they would not be detected by the usual microbiological tests. There are no analytical methods for these metabolites in tissues and, therefore, little is known as to their occurrence and persistence in tissues. There are no methods available for identifying residues of some commonly used B-lactam antibiotics including carbenicillin and ticarcillin. For cephapirin and ampicillin, except for one HPLC method for ampicillin in milk (79) only TLC procedures (72-74,76) with detection by bioautography are reported. 

Secretion. Some excretable substances are released into the urine by active transport in the renal tubules. These substances include and ions, urea, and creatinine, as well as drugs such as penicillin. 

Probenecid also inhibits the tubular secretion of most penicillins and cephalosporins and usually increases plasma levels by any route the antibiotic is given. Pharmacokinetics Probenecid is well absorbed after oral administration and produces peak plasma concentrations in 2 to 4 hours. It is highly protein bound (85% to 95%). Probenecid is excreted in the urine primarily as metabolites. 

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... 

Lactation Penicillins are excreted in breast milk in low concentrations use may cause diarrhea, candidiasis, or allergic response in the nursing infant. 

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