120 0.7 4 14 days PO Gavage 108 1.6 9 3 months PO 364 0.3 2 gavage 1038 1.25 7 Human [400 mg] Single PO 0.172 healthy dose volunteers # = animal:human plasma AUC0–24 h ; ND-not detected in plasma Table 7. Relative exposure to the fidaxomicin metabolites Tiacumicin C and F after oral fidaxomicin Species Study Dose Analyte AUC duration last exposure µg.h/mL ratio (number) Cmax AUC Dog 1038 a Tiacumicin C - - 3 months 0.174 beagle N PO Tiacumicin F 6 3 0.574 Human [400 Tiacumicin C steady ND ND healthy mg] state volunteers Tiacumicin F 0.172 PO (10 days) ND -not detectable. a not corrected for body weight during the study. The doses estimated in mg/kg using the weight recorded in Week 13: (♂ 10.3 kg, 8.4 kg) ♀: Table 8. Relative concentration of fidaxomicin and OP-1118 in the gastrointestinal tract in dogs versus humans Study Nominal Concentration in faeces µg/g Conc. ratio (dog: human) Dose mg/kg/day Fidaxomicin OP-1118 Fidaxomicin OP-1118 WIL609005 58 1418- 1880 28- 48 1-2 0.04 – 0.07 WIL609005 144 3595 - 8700 78 - 140 3-8 0.1-0.2 WIL609006 216 282- 5160 48 - 225 0.3-5 0.07-0.3 WIL609006 346 175 - 49 - 372 0.2 -35 0.07-0.5 WIL609005 461 7300 - 10920 118 - 214 7-10 0.2-0.3 WIL609007 824 5658 - 12050 84 - 159 5-11 0.1-0.2 WIL609006 1038 16985 - 219 - 1133 16-167 0.3-1.6 182500
14 days PO Gavage 120 0.7 4 3 months PO gavage 108 1.6 9 364 0.3 2 1038 1.25 7 Human healthy volunteers Single dose PO [400 mg] 0.172 # = animal:human plasma AUC0–24 h ; ND-not detected in plasma Table 7. Relative exposure to the fidaxomicin metabolites Tiacumicin C and F after oral fidaxomicin Species Study duration (number) Dose Analyte µg.h/mL AUC exposure ratio Cmax AUC Dog beagle PO 3 months 1038 a N Tiacumicin C 0.174 - - Tiacumicin F 0.574 6 3 Human healthy volunteers PO steady state (10 days) [400 mg] Tiacumicin C ND ND Tiacumicin F 0.172 ND -not detectable. a not corrected for body weight during the study. The doses estimated in mg/kg using the weight recorded in Week 13: (♂ 10.3 kg, ♀: 8.4 kg) Table 8. Relative concentration of fidaxomicin and OP-1118 in the gastrointestinal tract in dogs versus humans Study Nominal Dose mg/kg/day Concentration in faeces µg/g Conc. ratio (dog: human) Fidaxomicin OP-1118 Fidaxomicin OP-1118 WIL609005 58 1418- 1880 28- 48 1-2 0.04 – 0.07 WIL609005 144 3595 - 8700 78 - 140 3-8 0.1-0.2 WIL609006 216 282- 5160 48 - 225 0.3-5 0.07-0.3 WIL609006 346 175 - 49 - 372 0.2 -35 0.07-0.5 WIL609005 461 7300 - 10920 118 - 214 7-10 0.2-0.3 WIL609007 824 5658 - 12050 84 - 159 5-11 0.1-0.2 WIL609006 1038 16985 - 182500 219 - 1133 16-167 0.3-1.6 last