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 rec eived dosages equivalent to 0, 1, 2.5, 7.5 and 20 mg kg(-1) day(-1) fo r 204 or 205 days, Some animals were maintained without treatment for a recovery period of 29 or 30 days. 2 Clinical signs included poor coa t condition, weakness with impaired coordination, lethargy and other b ehavioural changes. There was also alimentary disturbance, and some de aths occurred at doses of 20 mg kg(-1) day(-1) and above. 3 Adverse ef fects upon body weight were seen although some recovery was apparent a fter the cessation of treatment. 4 Serum cholesterol concentrations we re reduced. Very large increases in serum ALT, AST and CK activities w ere recorded with CK-MM isoenzymes accounting for 80% or more of the t otal CK enzyme activity.