Penicillins administration route

Like penicillins, cephalosporins are (3-lactam antibiotics and interfere with bacterial cell wall synthesis. A very large number of cephalosporins are available for clinical use. They differ in their route of administration and clinical use. 

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. 

The rates of absorption, clearance, and elimination of penicillin G are further influenced by the route of administration. Intramuscular and subcutaneous injections provide drug to the bloodstream more slowly, but maintain concentrations longer than the intravenous administration. Absorption of penicillin G from intramuscular or subcutaneous sites can be further slowed down by the use of the relatively insoluble procaine salt. When equivalent dosages of penicillin G and procaine penicillin G were injected parenterally, peak residues concentration in blood occurred after 2 h and the drug had cleared the blood by 8 following penicillin G administration. With the procaine penicillin G, peak residues concentration appeared 5 h after injection and the drug cleared the plasma 24 h after administration (57). 

Although it is not a major elimination route following intravenous or intramuscular injection of penicillin G to dairy cattle, milk constitutes a very important route of elimination following intramammary injection since most of the dose enters milk (58, 59). The persistence of residues in milk does depend on the formulation and route of administration, but, in a wide variety of trials, residues were not found to persist beyond 5 days after the end of treatment (59, 60). Transfer of penicillin G from treated to untreated quarters has also been observed... 

Oxacillin and cloxacillin are the most widely used isoxazolyl penicillins, the latter being particularly appropriate for treatment or prevention of bovine staphylococcal mastitis. Following intramammary treatment of a lactating cow with three successive infusions of 200 mg/48 h each of sodium cloxacillin, residues were present in milk (detection limit equal to 3 ppb) from the treated quarter for 60 h after the last infusion crossover from treated to untreated quarter was also observed (59). When cloxacillin benzathine was administered by the intramammary route to dairy cows in the dry period at a dosage of 500 mg/quarter, cloxacillin residues were present neither in serum ( 25 ppb) sampled after 5 days of drug administration nor in milk ( 5 ppb), including the milk collected... 

Procedure Beta-lactam desensitization should be done in an intensive care unit and any concomitant risk factors for anaphylaxis, such as use of beta-blockers should be corrected. Protocols based on incremental use of the drug orally or parenterally have been described (190,193). The oral route is preferable and is associated with a lower incidence of adverse events, but mild transient reactions are frequent (171,194,195). Pregnant women with limited antibiotic choices have been treated with immunotherapy (196). Repeated administration will maintain a state of anergy, which is often lost after withdrawal (197). At the conclusion of therapy, patients must be informed that after withdrawal, they may once again become allergic to penicillin, with a new reaction to the first subsequent application (197). 

The solubility of a drug and the compatibility of a particular solvent with the site of injection are interrelated factors governing the suitability of this route of administration and the pharmaceutical formulation that is employed. The route of administration may also be governed by tolerability aspects associated with the formulation. If a drug cannot be dissolved in a concentrated manner in a suitable vehicle, then often dose size must increase. For example, intravenous injections of penicillin-type antibiotics are much more comfortable than when the same dose is administered intramuscularly. 

The pharmacology of penicillins differs markedly from compound to compound but has been well reviewed (57). The majority of derivatives, including penicillin G and the antipseudomonal penicillins, are unstable in gastric acid and are not available orally. The isoxazolyl penicillins are relatively acid stable but not consistently well absorbed by the oral route. Nafcillin and oxacillin are poorly absorbed orally cloxacillin, didoxacfllin, and flucloxacillin are more reliable. Penicillin V, ampicillin, and particularly amoxicillin are relatively well absorbed orally. Esters of ampicillin such as bacampicillin, pivampicillin, and talampicillin improve the level of oral absorption of ampicillin to that achieved by amoxicillin. Absorption can be diminished by food after oral administration, however, and peak blood levels, usually achieved after 1 to 2 h, are somewhat delayed after ingestion of food. 

Residues at the site of injection present specific problems. The persistence of residues at intramuscular injection sites may be due in part to the irritant response produced in the muscle. Chloramphenicol, tylosin, penicillins, dihydrostreptomycin and oxytetracycline have been shown to produce local irritation at the site of injection leading to residues persistence and this may be exacerbated by the solvent used (47-49) with one oxytetracycline product which produced little irritation, residues did not persist (49). Large variations in pharmacokinetic behaviour were noted in addition to the persistence at the injection site and in particular with oxytetracycline, bioavailability was reduced. These studies demonstrate the usefulness of pharmacokinetic data when studying specific routes of administration, and in particular they demonstrate the need to take into account other biological phenomena when attributing withdrawal periods, in this case, irritation at the injection site. The new draft EC Guideline requires that injection sites are examined in residues studies with injectable products and in the case of persistence at the site, then the withdrawal period will be based on this. 

Almost immediately after the introduction of penicillin to the clinic the value of the drug was evident. Different penicillins were developed with differing pharmacological properties, routes of administration, and spectrum of activities, but all penicillins worked in the same manner and required one particular chemical moiety, that being an intact beta-lactam ring (Figure 15.9). 

About one-third of an orally administered dose of penicillin G is absorbed from the intestinal tract under favorable conditions. Gastric juice at pH 2 rapidly destroys the antibiotic. The decrease in gastric-acid production with aging accounts for better absorption of penicillin G from the G1 tract of older individuals. Absorption is rapid, and maximal concentrations in blood are attained in 30 to 60 minutes. The peak value is approximately 0.5 unit/mL (0.3 pg/mL) after an oral dose of 400,000 units (about 250 mg) in an adult. Ingestion of food may interfere with enteric absorption of all penicillins, perhaps by adsorption of the antibiotic onto food particles. Thus oral penicillin G should be administered at least 30 minutes before a meal or 2 hours after. Despite the convenience of oral administration of penicillin G, this route should be used only in infections in which clinical experience has proven its efficacy. 

DICLOXACILLIN These semisynthetic penicillins are similar structurally and pharmacologically (Table 44-1). All are relatively stable in an acid medium and are absorbed adequately after oral administration. AU are markedly resistant to cleavage by penicillinase. These drugs are not substitutes for penicillin G in the treatment of diseases amenable to it and are not active against enterococci or Listeria. Oral administration is not a substitute for the parenteral route in the treatment of serious staphylococcal infections. 

Because of Its oheapness, mild infections with susoeptible microorganisms oan be treated with oomparatively large oral doses, although the most effective route of administration is parenteral, beoause fivefold the blood level oan be regularly achieved in this manner. As previously Indicated (see Clinically relevant chemical instabilities above), penicillin G is unstable under the acidic conditions of the stomaoh. 

Except for contact dermatitis, the route of administration appears to be of little importance in determining the type of hypersensitivity and clinical symptoms produced. Application of allergenic drugs to the skin is usually associated with a high incidence of sensitization (favorable conditions for the formation of conjugates ), whereas the oral route appears to be less likely to foster sensitization. Allergic reactions occur in about 2.5% of patients given penicillin G parenterally, in 5%... 

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