Pediatric erythromycins: a comparison of the properties of erythromycins A and B 2'-ethyl succinates.
The antibiotic erythromycin A is generally administered to children as a suspension of the pro-drug erythromycin A 2'-ethyl succinate. The success of the pro-drug depends on (a) elimination of the unacceptably bitter taste of free erythromycin, (b) its stability against stomach acid, and (c) its smooth (base-catalyzed) hydrolysis in the body to yield active erythromycin. We have investigated the rates and pathways of acid-catalyzed degradation and base-catalyzed hydrolysis of the 2'-ethyl succinates of erythromycins A and B. Esterification does not protect the drugs against acid-catalyzed degradation in solution; however, erythromycin B 2'-ethyl succinate is much more stable than the corresponding erythromycin A ester, degrading nearly 40 times more slowly. The rates of base-catalyzed hydrolysis in conditions mimicking the blood stream are similar for the two pro-drugs. We conclude that erythromycin B 2'-ethyl succinate is an attractive prospect as a pediatric erythromycin pro-drug.
Hassanzadeh
Abdolreza
A
Schools of Pharmacy and Pharmaceutical Sciences and Chemistry, University of Manchester, Oxford Road, Manchester, UK M13 9PL.
Gorry
Peter A
PA
Morris
Gareth A
GA
Barber
Jill
J
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002384:Catalysis; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D010372:Pediatrics; D011355:Prodrugs / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D011355:Prodrugs; C501700:erythromycin B 2'-ethyl succinate; D004917:Erythromycin