Penicillins acid-stable

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, ate unstable in gastric acid and ate not available orally. The isoxazolyl penicillins ate relatively acid stable but not consistendy well absorbed by the oral route. Nafcillin and oxacillin ate poody absorbed orally cloxacillin, dicloxacillin, and ducloxacillin ate more teUable. Penicillin V, ampicillin, and patticulady amoxicillin ate 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 adruinistration, however, and peak blood levels, usually achieved after 1 to 2 h, ate somewhat delayed after ingestion of food. 

The answer is b. (Hardman, p 1077.) Oxacillin is classified as a penicillinase-resistant penicillin that is relatively acid-stable and, therefore, is useful for oral administration. Major adverse reactions include penicillin hypersensitivity and interstitial nephritis. With the exception of methi-cillin, which is 35% bound to serum proteins, all penicillinase-resistant penicillins are highly bound to plasma proteins. Oxacillin has a very narrow spectrum and is used primarily as an anti staphylococcal agent... 

For years the most popular penicillin was a natural one, penicillin G, but it is not acid stable and is absorbed poorly through the intestine. Penicillin G can be hydrolyzed in the laboratory to 6-aminopenicillanic acid, which can... 

It has an antibacterial spectrum similar to benzyl penicillin but is less active. It is gastric acid stable and effective on oral administration. 

The degree of instability of the (3-lactam ring depends on the availability of the electrons for attack, so modification of penicillins with the addition of electron withdrawing groups near the amide carbonyl decreases the availability of these electrons and significantly improves acid stability. For example, the amino group of amoxicillin and ampicillin makes these molecules acid stable. 

Similar to Penicillin G (destroyed by p lactamase) but acid-stable and more active against gram-negative bacteria. Carbenicillin has -COONa instead of NH2 group. 

An isoxazolyl penicillin such as oxacillin, cloxacillin, or dicloxacillin, 0.25-0.5 g orally every 4-6 hours (15-25 mg/kg/d for children), is suitable for treatment of mild to moderate localized staphylococcal infections. All are relatively acid-stable and have reasonable bioavailability. However, food interferes with absorption, and the drugs should be administered 1 hour before or after meals. 

The pharmacology of penicillins differs markedly from compound to compound. The majority of derivatives, including penicillin (j and the antipseudomonal penicillins, are unstable in gastric acid and are not available orally. The isoxazolyl penicillins are relatively acid-stable but... 

Cephalothin i.s absorbed poorly from the gastrointestinal tract and must be administered parcntcrally for. systemic infections. It is relatively nontoxic and acid stable. It is excreted rapidly through tlie kidneys about 60% i.s lo.si within 6 hours of administration. Pain at the. site of intramuscular injection and thrombophlebitis following intravenous injection have been reported. Hypersensitivity reactions have been observed, and there is some evidence of cross-.scn.siti v-ity in patients noted previously to be penicillin sensitive. 

Doyle, F. P, Nayler, J. H., Smith, H., Stove, E. R. Some novel acid-stable penicillins. Nature 1961, 191, 1091-1092. 

The addition of precursors during the fermentation has thus far been very limited in scope, although the acid-stable penicillin V (phenoxymethylpenicil-lin) is produced by this method. This review deals principally with chemical alteration of the fermentation-produced antibiotic or intermediate. 

The discovery of penicillin by Alexander Fleming and its large-scale production, realized by the famous Oxford group of scientists and a consortium of US companies during World War II, has changed our life expectancy almost unbelievably. No wonder that the story of this great discovery has been told many times (e.g. [25]). In contrast, the story of the discovery of the first acid-stable, oral penicillin is less well known - in some of the various sources it is even neglected. 

Penicillin R Acid stable Penicillinase resistant Broad spectrum... 

The acylation of 6-APA with a,a-disubstituted aryl acetic acids yielded penicillins carrying a substituent on the a or benzylic carbon of the R side chain. Those of particular interest were penicillins carrying the polar -NH2 group (i.e., a-aminobenzyl penicillins) (Table 6-2, No. 13). The fact that this compound was acid stable and orally absorbed was not particularly novel (see penicillin V). Its antistaphylococcal activity was 25-60% less than that of penicillin G (the D-isomer was more active than the racemic d, l). However, its antibacterial spectrum was dramatically different. Ampicillin s spectrum, unlike previous penicillins, encompassed many important Gm- bacteria. Species of Hemophilus, Proteus, Salmonella, Shigella, and Escherichia succumbed to ampicillin. Even though resistant... 

Penetrate cell membranes poorly or not at all limited or no significant absorption from GIT except for acid-stable aminopeni-cillins, which have moderate but species-variable absorption distribution limited mainly to extracellular fluids concentrations in intracellular fluid, CSF, miUc, and ocular fluids low, but effective concentrations may be reached in synovial, peritoneal, and pleural fluids some penicillins actively transported out of CSF into plasma generally excreted, usually in urine, in high concentrations as the parent molecule some drugs actively secreted into urine and/or bUe biotransformation (e.g., in the liver) usually slight or absent... 

Apothecon product, Veetids, an acid-stable oral form of penicillin, was seventh most pharmacy-presctibed antibiotic in United States in 1995. 

The antibiotics of the penicillin group (D 23.3), for instance, during evolution were optimized to act in the natural habitat, but not to pass the human stomach with its low pH-value. As a result they are unsufficiently stable to hydrolysis. Hence natural penicillins cannot be used orally, e.g., in tablets, a drawback which in the meantime has been overcome by the synthetical preparation of acid stable derivatives. 

It certainly does. For one thing the earliest penicillins like benzylpenicillin (penicillin G) are decomposed by acid. The contents of our stomachs are strongly acidic, so that these penicillins could not be taken orally but had to be iryected. It was found that when phenoxyacetic acid was added to the fermentation broth, the resulting phenoxymethylpenicillin, commonly known as penicillin V, was fairly acid-stable and could be taken by mouth. Subsequently many more oral penicillins like this have been developed. 

---