Erythromycin intestinal absorption

Cholestatic hepatitis, which is associated primarily with erjdhromycin estolate, can be caused by all forms of erythromycin, including the base, estolate, ethylsuccinate, propionate, and stearate (39,41). Although it was originally speculated that a hypersensitivity reaction to the estolate ester rather than to the erjdhromycin itself was responsible for this adverse reaction (42), erythromycin does inhibit bile flow (43). Most probably the differences in hepatotoxicity between the various erythromycin derivatives are of a quantitative rather than a qualitative nature (44,45), perhaps because of better intestinal absorption of the estolate. Potentially severe but rare cholestatic liver injury occurs in perhaps up to 2-4% of... 

A single-dose study in 8 healthy subjeets found that the AUC and serum levels of talinolol 50 mg were inereased by 51% and 26%, respectively, by erythromycin 2 g. It was suggested that the increased bioavailability of talinolol was due to inereased intestinal absorption caused by the inhibition of P-glycoprotein by erythromycin. ... 

A complication here, however, is noted with those drugs that exhibit a limited chemical stability in either acidic or alkaline fluids. Since the rate and extent of degradation is directly dependent on the concentration of drug in solution, an attempt is often made to retard dissolution in the fluid where degradation is seen. There are preparations of various salts or esters of drugs (e.g., erythromycin) that do not dissolve in gastric fluid and thus are not degraded there but which dissolve in intestinal fluid prior to absorption. A wide variety of chemical derivatives are used for such purposes. 

Erythromycin (XX) is labile at pH values below pH 4, and hence is unstable in the stomach contents. Erythromycin stearate (the salt of the tertiary aliphatic amine and stearic acid), being less soluble, is not as susceptible to degradation. The salt dissociates in the intestine to yield the free base, which is absorbed. There are differences in the absorption behaviour of the erythromycin salts and differences in toxicity, which may be related to their aqueous solubilities. Erythromycin ethylsuccinate was originally developed for paediatric use because its low water solubility and relative tastelessness were suited to paediatric formulations. The soluble lactobionate is used in intravenous infusions. 

Erythromycin formulations are highly irritant if administered by i.m. injection and are not used in horses. Many p.o. preparations of erythromycin are enteric coated to allow passage into the small intestine, where absorption is higher because of the higher pH. In horses, erythromycin stearate and erythromycin phosphate produce peak plasma concentrations faster than the ester formulations following p.o. administration. 

Absorption Erythromycin base is incompletely but adequately absorbed from the upper small intestine. Because it is inactivated by gastric acid, the drug is administered as enteric-coated tablets, as capsules containing enteric-coated pellets that dissolve in the duodenum, or as an ester. Food may impair absorption. Esters of erythromycin base e.g., stearate, estolate, and ethylsuccinate) have improved acid stability and are less affected by food. Higher erythromycin concentrations can be achieved by intravenous administration. 

Edelbroek MAL, Horowitz M, Wishart JM, Akkermans LMA. Effects of erythromycin on gastric emptying, alcohol absorption and small intestinal transit in normal subjects. J Nucl Med (1993) 34, 582-8. 

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