Preclinical toxicological studies of carbidopa and combinations of carbidopa and levodopa

Carbidopa was administered po at 25, 45 and 135 mg/kg/day to monkeys for up to 1 year and to rats for up to 96 weeks. No physical signs were produced in monkeys although rats exhibited flaccidity at all dosage levels. No deaths, weight changes, or changes in the results of ophthalmologic, hematologic, or pathologic examinations were produced in either species. Carbidopa given to dogs resulted in pyridoxine deficiency, which was prevented by coadministration of pyridoxine. Rats and monkeys were given combinations of carbidopa and levodopa ($\text{10}\text{20}\text{,}\text{10}\text{50}\text{,}\text{and}\text{10}\text{100}\text{mg/kg/day}$). Rats given the highest dosage level daily for 2 years exhibited decreased activity, ptyalism, and retardation of weight gain. Some evidence of temporary salivary gland acinar hypertrophy was also noted. Increased activity at the middle and high dosage levels was noted in monkeys given the combined drugs for one year. No other physical signs or ophthalmologic, hematologic, or pathologic changes were noted. Carbidopa inhibits extracerebral decarboxylase activity so that lower doses of levodopa can be used in treatment of Parkinsonism with a reduction in side effects.