Systemic efficacy on Cryptosporidium parvum infection of aminoxanide (RM-5061), a new amino-acid ester thiazolide prodrug of tizoxanide.

摘要: Cryptosporidiosis is a gastrointestinal illness with profuse diarrhoea. Although there are no other Food and Drug Administration (FDA)-approved alternatives for the treatment of cryptosporidiosis, nitazoxanide (NTZ) can be qualified as partially effective. In immunosuppressed conditions, severe and/or disseminated cryptosporidiosis may occur patients should treated parenterally. To achieve goal developing parenteral current study was undertaken to investigate in vitro vivo anticryptosporidial activity aminoxanide. This new l-tert-leucyl thiazolide soluble prodrug tizoxanide (TIZ), main metabolite NTZ. Confirming good efficacy aminoxanide Cryptosporidium parvum-infected HCT-8 cells 50% inhibitory concentration 1.55 μm (±0.21), C. Mongolian gerbils (Meriones unguiculatus), 5-day daily intramuscular dose 100 mg kg−1 resulted 72.5% oocyst excretion inhibition, statistically equivalent 75.5% 4-fold lower oral parvum-induced intestinal pathology inflammation were improved. Aminoxanide provides an injectable form TIZ that NTZ unable do promising drug which optimization formulation further explored. These results represent first step towards cryptosporidiosis.