Ampicillins ester

Worldwide retail antibiotic sales in 1986 were approximately 11 biUion of which penicillins comprised approximately 2.5 biUion (66). Preparations containing ampicillin are estimated at 800 million whereas those containing amoxicillin are estimated at 1,020 million. Total sales include sales of ampicillin esters and the iireidopenicillins derived from ampicillin. Total sales of penicillins, including semisynthetic penicillins in the United States in 1987, were 25 million (67). Sales of amoxicillin, the largest single selling penicillin, were approximately 350 million. 

Pro-drugs (e.g. earbenicillin esters, ampicillin esters Fig. 5.2, Table 5.1) are hydrolysed by enzyme aetion after absorption from the gut mucosa to produce high blood levels of the aetive antibiotic, earbenicillin and ampicillin, respectively. 

Contra Toxic D convulsive disorder Disp Liq SE BP, sedation, constipation Interactions Effects OF ampicillin esters, azole antifungals, Fe salts EMS ... 

Contra Toxic D convulsive disorder Disp Liq SE 4- BP, sedation, constipation Interactions X Effects OF ampicillin esters, azole antifungals, Fe salts EMS Concurrent EtOH use can T sedation contains anhydrous morphine from opium OD May cause constipation and CNS depression activated charcoal may be effective, naloxone can be used for resp depression... 

In horses, amoxicillin or ampicillin sodium are well absorbed following i.m. or s.c. administration. Amoxicillin or ampicillin trihydrate are poorly soluble salts that are given i.m. and produce lower plasma concentrations that extend over a longer period of time. Amoxicillin and ampicillin are too poorly absorbed following p.o. administration to be clinically useful in horses. The ampicillin esters, pivampicillin and bacampicillin, show promise for p.o. use but are currently not available for use in horses. 

Chronic treatment with omeprazole decreases the absorption of vitamin B12, but the clinical relevance of this effect is not clear. Loss of gastric acidity also may affect the bioavailability of such drugs as ketoconazole, ampicillin esters, and iron salts. 

Cephalexin esters (179) rearrange via intramolecular nucleophilic attack of the side-chain amino-group to give the piperazinedione (180). That a similar reaction does not take place with ampicillin esters is explained by steric hindrance to intramolecular attack. 

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. 

An alternate route to ampicillin not only circumvents the need for 6-APA but also has the advantage of providing a prodrug form of ampicillin as well as the parent compound. Reaction of benzylpenicillin (4) with the acid protecting group, 29, gives the formol ester, 30. Reaction of the product with phosphorus pentachloride leads to the corresponding imino chloride (31). 

Sarpicillin (10) is a double prodrug of ampicillin in that not only is the carboxy group masked as an ester, but a... 

Selection of the most suitable chemical form of the active principle for a tablet, while not strictly within our terms of reference here, must be considered. For example, some chloramphenicol esters produce little clinical response [13], There is also a significant difference in the bioavailability of anhydrous and hydrated forms of ampicillin [14], Furthermore, different polymorphic forms, and even crystal habits, may have a pronounced influence on the bioavailability of some drugs due to the different dissolution rates they exhibit. Such changes can also give rise to manufacturing problems. Polymorphism is, of course, not restricted to active ingredients, as shown, for example, in an evaluation of the tableting characteristics of five forms or sorbitol [15]. 

In attempts to improve the oral activity of norfloxacin, prodrug techniques have been employed. In an initial approach, the (5-methyl-2-oxo-l,3-diox-4-yl)-methyl group, which had been shown previously to be effective in a novel ampicillin prodrug, was investigated as a promoiety [ 109]. However, although the ester (77) liberates norfloxacin in the presence of mouse blood, after oral administration to mice, it was found that the blood levels of norfloxacin achieved are lower (approximately with respect to Cmax) than those achieved upon oral administration of an equimolar dose of norfloxacin, itself. This observation has been assumed to be due to an instability of this ester prior to absorption rather than an inability to liberate the parent drug after absorption. 

A few well-established prodrugs contain an (acyloxy)methyl or an [(alkoxycarbonyl)oxy]methyl group. Classical examples of the former are two prodrugs of /1-lactam antibiotics, namely pivampicillin (8.50), the (pivaloyloxy)methyl ester of ampicillin, and cefuroxime axetil (8.51), the... 

Prodrugs are drug substances that are biotransformed in the body to active metabolites and chemotherapeutic agents. Examples include sulfasalazine to sul-fapyridine, phenylbutazone to oxy-phenbutazone, aspirin to salicylate, and heta-cillin to ampicillin. In some cases, such as aspirin (ester) and hetacillin (amide), hydrolysis in water releases the active drug moiety contained within the basic structure of the prodrug. 

---