ABSTRACT
The design of this 6-month study is shown in Table 18.16. These wild caught monkeys, weighing between 2.5 and 4.1 kg, were housed singly in stainless-steel cages with a mesh front and floor and a sliding back wall for squeeze-cage removal of the animals. The ambient temperature was at 22° C, with a light cycle of 12 h light/12 h darkness. Monkey chow (Piccioni, Italy) was provided in rations equivalent to 4% body weight, in two portions daily, with fruit twice a week; water was available ad libitum. The plasma drug levels are shown in Table 18.17 and demonstrate comparatively high levels in this primate compared, dose for dose, with marmosets. All animals in the highest dose group (80 mg kg-1) died before completion of the test and also all males and two of the four females at the next highest dose level (50 mg kg - 1); the onset of death was sudden, preceded by lethargy and subdued behaviour. No effects were seen in AP and ALT levels, but an increase in liver weight (of approximately 25%) was seen in the animals dosed at 25 mg kg-1 which survived to the end of the 6-month dosing period (Table 18.18). There were no histological changes in the liver attributable to treatment, and deaths at the two higher doses were due to renal tubular necrosis (data not shown).
