TOXICITY OF A NOVEL HMG-COA REDUCTASE INHIBITOR IN THE COMMON MARMOSET (CALLITHRIX-JACCHUS)

1 GR95030X, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was administered daily to marmosets by gavage. In a Maximum Repeatable Dose (MRD) study, doses of up to 30 mg kg(-1) day(-1) were administered for 49 days. In a chronic study, animals received dosages equivalent to 0, 1, 2.5, 7.5 and 20 mg kg(-1) day(-1) for 204 or 205 days, Some animals were maintained without treatment for a recovery period of 29 or 30 days. 2 Clinical signs included poor coat condition, weakness with impaired coordination, lethargy and other behavioural changes. There was also alimentary disturbance, and some deaths occurred at doses of 20 mg kg(-1) day(-1) and above. 3 Adverse effects upon body weight were seen although some recovery was apparent after the cessation of treatment. 4 Serum cholesterol concentrations were reduced. Very large increases in serum ALT, AST and CK activities were recorded with CK-MM isoenzymes accounting for 80% or more of the total CK enzyme activity.