Influence of the dopamine agonist alpha-dihydroergocryptine on the pharmacokinetics of levodopa in patients with Parkinson's disease.
This study investigated whether chronic coadministration of alpha-dihydroergocryptine (DHEC) altered the plasma pharmacokinetics of individualized treatments with levodopa in 12 patients with Parkinson's disease. Steady-state pharmacokinetics of plasma levodopa (L-Dopa) under combined treatment were compared with those under treatment with L-Dopa alone. There was no evidence of increased exposure to L-Dopa caused by concomitant treatment with DHEC. In contrast, additional treatment with DHEC reduced the overall exposure to L-Dopa (17.5% reduction in area under the curve; 95% CI: 23%-6%). This effect was small but statistically significant for the area under the plasma concentration-time curve, whereas tmax (time of maximum plasma concentration) and peak-to-trough fluctuation were not affected. Cmax (maximum plasma concentration), on average, was reduced to a similar extent (-14.5%; 95% CI: 38% to -17%), albeit not significantly. The magnitude of the interaction does not suggest changing the current clinical practice of up-titrating DHEC and subsequently adapting L-Dopa to the individual needs of patients.
Minea
D
D
Department of Neurology, University of Transsilvania, Braşov, Romania.
Varga
I
I
Falup-Pecurariu
C
C
de Mey
C
C
Retzow
A
A
Althaus
M
M
D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016001:Confidence Intervals; D025443:Dihydroergocryptine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007980:Levodopa / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood* / Q000188:drug therapy
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D007980:Levodopa; D025443:Dihydroergocryptine