A comparative study on the effect of erythromycin and ivermectin on abomasal emptying in Holstein-Friesian calves Motilides namely erythromycin have a great ability to increase abomasal emptying rate. The aim of this study was to evaluate the abomasal emptying rate in calves receiving either erythromycin or ivermectin. Five male Holstein-Friesian calves were given each of the following 4 treatments in random order: Control, 2 mL of 0.9% NaCl IM, erythromycin, 8.8 mg/kg IM, ivermectin, 200 ug/kg IV. Abomasal emptying rate was assessed by acetaminophen absorption. Calves were fed 2 L of cow milk containing acetaminophen (50 mg/kg body weight) 30 min after each treatment was administered and jugular venous blood samples were obtained periodically after suckling. The maximum observed plasma concentration (Actual Cmax) and time of maximum observed plasma concentration (Actual Tmax) were obtained from a plot of the plasma acetaminophen concentration versus time data. Non linear regression analysis was used to model the plasma acetaminophen concentration-time relationship and calculate Model Cmax and Model Tmax. The results showed that administration of ivermectin could increase the abomasal emptying rate but to a lesser extent compared to erythromycin. Also the increase in plasma glucose after administration of ivermectin was comparable to erythromycin. The study also revealed that ivermectin unlike other motilides in spite of lacking a dimethylamino group could affect the gastrointestinal motility. This might imply that ivermectin exerts its effect via a different route other than affecting motilin receptors, or may question necessariness of dimethy amino group for the promotility effects.

Esterification of the 2`-position of erythromycin proved to be facile and to lead to compounds that were essentially tastefree, and somewhat resistant to acid. These 2`-esters were found to exhibit very little antibacterial activity, thus requiring activation by hydrolysis to the parent drug. Erythromycin B is a biosynthetic precursor of erythromycin A. Although it has similar in vitro antibacterial activity to erythromycin A, it has not yet found a place as an independent drug. The marketleading paediatric erythromycin, erythromycin A 2`-ethyl succinate, is undoubtedly effective in the treatment of infections in children, but there is surprisingly little published data on its stability at acidic pH resembling the stomach. We compared the acid-catalyzed degradation of erythromycins A and B 2`-ethyl succinates, and also the rates of hydrolysis of the two pro-drugs to their parent erythromycins by using NMR techniques. Erythromycin B is inherently much more stable to acid. The half-lives of erythromycin B at various acidic pHs were found 110-200 times greater than those of erythromycin A. Interestingly, here, esterification with an ethyl succinyl group provided no additional protection against acid; on the contrary the ester actually degraded somewhat faster than the parent drug (2.7 times). This study also showed that in the case of erythromycin A ethyl succinate the protection strategy against acid afforded by the ester is quite small- degradation was slowed by a factor of about 2. Erythromycins and their derivatives all equilibrate with the corresponding enol ether in acidic solution. Our results show that for erythromycin B the equilibrium lies on the side of the erythromycin ketone. This is still more emphatically the case when the erythromycin is deuteriated at C8. However, when erythromycin A is treated with acid, its enol ether accumulates (the presence of deuterium in the buffer notwithstanding) and after time is in large excess over erythromycin A. Clearly the equilibrium lies well on the side of the enol ether. Esterification makes little difference to the position of equilibrium. This result is of great potential importance because these compounds have potent gut motilide activity, especially associating with enol ether formation. We can see that enol ether formation is suppressed in erythromycin B and its derivative, and we would expect these compounds to exhibit reduced gut motilide activity. Our results suggest that erythromycin B ethyl succinate shows similar but slightly better hydrolysis characteristics to erythromycin A ethyl succinate. The half-life to hydrolysis was 25% shorter at 37 ºC but 10% longer at room temperature under our conditions. It is important for antibacterial activity that erythromycin esters are hydrolyzed at a reasonable rate in the body; it is almost equally important that hydrolysis is suppressed in the medicine bottle. Hydrolysis yields the vile-tasting erythromycin, which makes the drug intolerable to some children. Overally these data suggest that erythromycin B esters may be superior to erythromycin A esters in pediatric use. Pre-clinical and clinical trials are required to determine whether these chemical advantages prove to be decisive in the clinic.