The influence of levodopa in the pharmacokinetics of bromocriptine in Parkinson's disease

The administration of bromocriptine in addition to levodopa in Parkinson's disease produces beneficial results. Several hypotheses have explained the advantage of the combined treatment by a pharmacodynamic interaction in the striatum. However, no study has considered the possibility that levodopa modifies the kinetics of bromocriptine. In the present study performed with parkinsonian patients, we measured blood levels of bromocriptine (by radioimmunoassay) at 0, 30, 60, 90, 120, 180, and 240 min after the oral administration of bromocriptine alone and together with 250 mg levodopa plus 25 mg DCI. After loading of bromocriptine alone, we found mean peak levels at 60 min (1.42 ng/ml) and at 90 min (1.82 ng/ml). These values were reduced by levodopa (0.97 ng/ml at 60 min and 0.93 ng/ml at 90 min). Although we did not observe substantial clinical differences among the groups after the drug challenge (Webster scale), this study supports our previous findings and suggests that one of the advantages of a combined treatment may result from a modification of the plasma levels of bromocriptine by levodopa. A 'smoothing' of the plasma bromocriptine curve possibly avoids sudden oscillations of the drug and enables a more 'stable' penetrability of the medication into the central nervous system. Therefore long-term combined treatment is advised in preference to bromocriptine alone.