2.9. Maximum Tolerated Dose Determination

In order to determine the maximum dose of JT09 that can be tolerated, its dose level was increased until the maximum tolerated dose (MTD) was identified or, if MTD dose was not reached, the maximum-administered dose (MAD) (Le Tourneau et al., 2010). The MTD is a dose that does not produce mortality, a loss of more than 10% body weight, or overt signs of toxicity. Six rats were included at each dose level (50, 70, and 90 mg/kg, p.o.). The animals were observed twice daily; body weights and detailed clinical observations for behavioral toxicity (porphyrin staining, changes in activity levels, changes in grooming habits, convulsions, catalepsy, muscular rigidity, and excessive vocalization) were made daily for 4 days after dosing at each level. Doses were chosen based on the compound’s ED₉₀ for analgesic potency.