Bromocriptine blood levels after the concomitant administration of levodopa, amantadine and biperiden in Parkinson's disease

We recently demonstrated that when different drugs (mainly used for the treatment of Parkinson's disease) are administered in combination they interfere with the availability of bromocriptine in the brain of rats (striatum and hypothalamus). In the present study performed with parkinsonian patients, we measured plasma levels of bromocriptine (RIA) over 4h after giving orally 5 mg bromocriptine alone; together with levodopa 250 mg plus 25 mg DCI (10 patients); with 100 mg amantadine HC1 (5 patients) and with biperiden 5 mg (5 patients). Amantadine and biperiden did not interfere with the pharmacokinetics of bromocriptine. However, levodopa significantly diminished plasma levels (a mean increment of 1.78 mg ± 0.30 vs 0.92 ± 0.18 mg/ml). We postulate that levodopa may interfere with the metabolism of bromocriptine in the liver. Although we did not observe substantial clinical differences among the patients (Webster scale), this study supports our previous findings and suggests that one of the advantages of 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 availability and enables a more “stable”penetrability of the medication into the central nervous system.