In vivo expression of in vitro anticoccidial activity.
Large-scale screening has led to the identification of several experimental compounds that have very potent intrinsic activity against coccidia, but the lack of translation to in vivo efficacy has been a major hurdle in developing such leads into effective new drugs. We developed methods to explore the impact of oral availability and appropriate distribution in tissue, both of which are potentially important factors in the expression of activity in vivo. For the compounds that we examined, neither oral absorption nor distribution to the site of infection appeared to be the critical barrier to in vivo expression of intrinsic anticoccidial activity. Elucidation of the nature of additional factors that might be involved could assist greatly in the identification of useful new anticoccidial agents.
Ricketts
A P
AP
Central Research Division, Pfizer Inc., Groton, Connecticut 06340.
Olson
J A
JA
Rice
J R
JR
D000284:Administration, Oral; D000818:Animals; D002645:Chickens; D003048:Coccidiosis / Q000188:drug therapy*; D003049:Coccidiostats / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003667:Decoquinate / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D016786:Eimeria tenella / Q000187:drug effects*; D007260:Infusion Pumps; D011799:Quinazolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D052999:Quinazolinones; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution; D014227:Triazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000096926:Benzenesulfonamides
D003049:Coccidiostats; D003667:Decoquinate; D011799:Quinazolines; D052999:Quinazolinones; D013449:Sulfonamides; D014227:Triazines; C078054:CP 60949-4; C078053:CP 30542; D000096926:Benzenesulfonamides