Mfp was obtained as pure substance from Sigma (M8046) or as tablet formulation Mifegyne (200 mg/tablet; Mfp content confirmed by high-performance liquid chromatography [HPLC] with diode array detection, see below) from Nordic Pharma. Rtv was obtained from AbbVie as Norvir 100 mg. Mfp and Rtv were either diluted in DMSO for i.p. application or suspended in ASV (0.9% NaCl [w/v], 0.5% carboxymethyl-cellulose MW 250.000 [w/v], 0.4% polysorbate 80 [v/v], 0.9% benzyl alcohol [v/v]). Mfp was also used as suspension in sesame oil.
Drug dosages applied to rats and monkeys can be converted to HEDs according to the FDA-approved body surface area (BSA) normalization approach.48 ,49 (link) Specifically, calculating results in the following conversion factors: for rats weighing 250 g, monkeys weighing 3 kg, and an assumed human weight of 70 kg: rat dosage (e.g., 50 mg/kg) × 0.156 = HED (7.8 mg/kg); monkey dosage (e.g., 50 mg/kg) × 0.357 = HED (17.9 mg/kg). In addition, it must be considered that bioavailability of Mfp in monkeys (15%) is considerably lower compared to humans and rats (40%),19 justifying higher dosages to be applied in monkeys as compared to rats.
Drug dosages applied to rats and monkeys can be converted to HEDs according to the FDA-approved body surface area (BSA) normalization approach.48 ,49 (link) Specifically, calculating results in the following conversion factors: for rats weighing 250 g, monkeys weighing 3 kg, and an assumed human weight of 70 kg: rat dosage (e.g., 50 mg/kg) × 0.156 = HED (7.8 mg/kg); monkey dosage (e.g., 50 mg/kg) × 0.357 = HED (17.9 mg/kg). In addition, it must be considered that bioavailability of Mfp in monkeys (15%) is considerably lower compared to humans and rats (40%),19 justifying higher dosages to be applied in monkeys as compared to rats.