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

Abstract

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.

Lack of Pharmacokinetic Interactions Between Transdermal Rotigotine and Oral Levodopa/Carbidopa

“…17 A significant decrease of bromocriptine plasma levels, which may result from an interference of levodopa comedication with bromocriptine metabolism in the liver, has been reported. 18 Low (1.5 mg/d) and high (4.5 mg/d) pramipexole doses administered concomitantly with levodopa did not alter levodopa bioavailability in a double-blind, placebo-controlled trial. 19 There was no pharmacokinetic interaction reported under coadministration of ropinirole and levodopa in PD patients not previously treated with dopamine agonists.…”

“…On the other hand, it has been shown that chronic bromocriptine therapy has no effects on levodopa pharmacokinetics in patients with Parkinson disease 17 . A significant decrease of bromocriptine plasma levels, which may result from an interference of levodopa comedication with bromocriptine metabolism in the liver, has been reported 18 …”