Penicillin absorption, oral

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. 

One of the most popular orally active penicillins in present clinical use is amoxicillin (12). Its oral effectiveness and broad spectrum of activity against common pathogens as well as its better absorption than its closest precedent competitor, ampicillin (14), largely accounts for this. Higher blood and tissue levels of antibiotics is another means of dealing with resistance. In an attempt to achieve yet further improvements in oral bioavailability and hence blood and ti.ssue levels of amoxicillin, the prodmg fumoxicillin (13) is prepared from amoxicillin (12) by treatment with furfural [3]. The imine moiety is less basic than the primary amine so that the isoelectric point of fumoxicillin is more on the acid side than is that of amoxicillin. 

Absorption - Peak serum levels occur approximately 1 hour after oral use. Parenteral penicillin G (sodium and potassium) gives rapid and high but transient blood levels derivatives provide prolonged penicillin blood levels with IM use. 

Sulfasalazine can inhibit the absorption of cardiac glycosides and folic acid. It may displace certain drugs, including warfarin, phenytoin, methotrexate, tolbutamide, chlorpropamide, and oral sulfonylureas, from their protein binding sites. Sulfasalazine can diminish the effectiveness of penicillins and estrogen-containing oral contraceptives. 

Oral nafcillin absorption is erratic (consider alternate oral penicillinase-resistant penicillins)... 

After oral administration, benzyl penicillin is destroyed by gastric acid. It is mainly absorbed from the duodenum. It is absorbed in aqueous solution rapidly after intramuscular or subcutaneous administration. Penicillin is widely distributed in the body after absorption and approximately 60% of plasma penicillin is bound to albumin. The major... 

Amoxycillin is a semisynthetic penicillin, a close congener of ampicillin and active against gram positive and negative organisms. Its absorption is more complete than ampicillin. Food does not interfere with its absorption. Its absorption after oral administration is complete hence less incidence of diarrhoea. It is eliminated in urine in unchanged form. 

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. 

Most oral preparations are solid dosage forms that need to be dissolved before they can be absorbed. The inert ingredients of such dosage forms can have a profound effect on the dissolution of the active ingredient and thereby control its rate of absorption. In addition, the drug may be unstable in the gastrointestinal fluids, as in the case of penicillin G, or metabolized. 

Kanamycin is an aminoglycoside complex produced by Streptomyces ka-namyceticus. It is comprised of three components, kanamycin A being the major component and kanamycins B and C minor congeners. Kanamycin is active against many pathogenic bacteria and has been used parenterally for treatment of bovine respiratory disease, mastitis, and other infectious conditions. A popular combination used in horses and cattle with respiratory disease is kanamycin and penicillin G. It is also used orally for treatment of bacterial enteritis because limited absorption occurs after oral administration. 

Dicloxacillin is absorbed well from the gastrointestinal tract but the presence of food in the stomach reduces resorption. Although cloxacillin differs chemically from oxacillin only in the presence of a chlorine atom, their absorption profile after oral administration is not similar. Cloxacillin is more rapidly and effectively absorbed than oxacillin. However, absorption of all isoxazolyl penicillins is better when given by intramuscular injection. These agents can be also administered by intravenous, intrauterine, intra-articular, intrapleural, and intramammary injections. 

Methicillin is a semisynthetic penicillin that also resists the action of -lactamases and, thus, is frequently used for penicillin G-resistant staphylococci. It is the first semisynthetic penicillin developed but it is poorly absorbed when given orally due to its instability in gastric acid. Absorption is better when it is administered intravenously or intramuscularly. Methicillin is principally eliminated in the urine but small amounts are also found in bile and other body fluids. 

In dogs, absorption following oral administration tends to be poor. At similar oral doses, peak serum levels are lower and plasma levels are less persistent than those observed for methicillin. Following intramuscular administration, however, maximum concentrations in serum are reached within 30 min. In contrast to methicillin, liver is the main excretory pathway for nafcillin. Like most other penicillins, nafcillin undergoes biotransformation to a small extent. Parent compound and its metabolites are excreted in bile and urine. Concentrations of nafcillin in tissues tend to be higher and more persistent following parenteral administration than was the case for methicillin, obviously due to enterohepatic recirculation. 

Neomycin Neomycin interferes with the absorption of digoxin, methotrexate, vitamins, some penicillins, acarbose, and oral contraceptives. 

Several natural penicillins can be produced, depending on the chemical composition of the fermentation medium used to culture penicillium. Penicillin G (benzylpenicillin) has the greatest antimicrobial activity of these natural penicillins and is the only natural penicillin used clinically. However, penicillin G is not stable it is extremely acid-labile. Only about one-third of an oral dose is absorbed under the most ideal conditions. Therefore, it is generally not given orally but is administered by intramuscular injection. Several newer derivatives of penicillin G have been developed that do have good to excellent oral absorption (e.g., cloxacillin, ampicillin, and amoxicillin). 

Absorption Most of the penicillins are incompletely absorbed after oral administration and reach the intestine in sufficient amounts to affect the composition of the intestinal flora. However, amoxicillin is almost completely absorbed. Consequently, it is not appropriate therapy for the treatment of shigella- or salmonella-derived enteritis, since therapeutically effective levels do not reach the organisms in the intestinal crypts. Absorption of penicillin G and all the penicillinase-resistant penicillins is decreased by food in the stomach since gastric emptying time is reduced and the drugs are destroyed in the acidic environment. Therefore, they must be administered 30-60 minutes before meals or 2-3 hours postprandially. Other penicillins are less affected by food. 

Estimates of bioavailability of penicillin V following oral administration range from 25% to 60%. Penicillin V should be administered an hour before food or on an empty stomach. Administration with food decreases the peak serum concentration but does not affect overall absorption of the drug. 

Acid resistance permits oral administration, provided that enteral absorption is possible. All derivatives shown in (B) can be given orally. Penicillin V (phenoxyme-thylpenicillin) exhibits antibacterial properties similar to those of penicillin G. 

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