CLINICAL AND PHARMACOKINETIC EVALUATION OF L-DOPA AND CABERGOLINE COTREATMENT IN PARKINSONS-DISEASE

Previous investigations on the mutual pharmacokinetic influence of L-d opa and dopamine agonists in Parkinson's disease (PD) have shown contr oversial results. Two studies of the possible clinical and pharmacokin etic interaction between L-dopa and cabergoline were performed in 10 p atients with de novo PD and 12 patients with fluctuating PD. In the fi rst study (de novo patients), cabergoline was administered at increasi ng dosages until the maximum dosage of 2 mg/day once a day for 8 weeks ; subsequently L-dopa (250 mg/day) was added. Blood levels of cabergol ine were assayed in two different days, before starting L-dopa, and 1 week thereafter. In the second 8-week study (fluctuating patients), ca bergoline was added to the current L-dopa therapy (maximum dosage 4 mg /day once a day). Blood levels of L-dopa were measured in two differen t days, before cabergoline was added, and at the end of the study. In both studies motor performance was evaluated by means of the Unified P arkinson's Disease Rating Scale (motor examination) and the Clinical G lobal Impression Scale; on-off diaries of daily motor condition also w ere filled by fluctuating patients. In patients with de novo PD, caber goline pharmacokinetic parameters were unmodified by the adjunct of L- dopa, except that the time ro reach the peak concentration (T-max) sig nificantly increased after L-dopa. in patients with fluctuating PD, no modification of L-dopa pharmacokinetics was observed before and after cabergoline coadministration. Clinical evaluations confirmed that cab ergoline is effective in the treatment of advanced PD as well as in th e management of de novo patients.