Influence of the Dopamine Agonist α-Dihydroergocryptine on the Pharmacokinetics of Levodopa in Patients with Parkinson's Disease

Abstract

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.

Levodopa availability improves with progression of Parkinson’s disease

“…The hospitalised PD patients only received one tablet, which contained 100 mg levodopa and 25 mg benserazide [Madopar LTÒ], at 6.30 a.m. after an overnight fasting and without additional intake of their regular antiparkinsonian compounds for at least 12 hours [16,30]. We dissolved this only in Europe available levodopa/benserazide dispersible formulation in 100 ml water immediately before administration [5].…”

“…To date, most studies on levodopa plasma levels investigated the pharmacokinetic behaviour of various available standard and sustained release levodopa preparations mostly in healthy volunteers or early patients with Parkinson's disease (PD) [6,31]. However, chronic antiparkinsonian drug intake may alter levodopa metabolism and thus appearance in plasma [16,31]. Further important influencing factors are concomitantly applied: anticholinergic antiparkinsonian drugs, alterations of the large neutral amino acid gastrointestinal transport system and gastric emptying velocity [16,17,29,31].…”

“…However, chronic antiparkinsonian drug intake may alter levodopa metabolism and thus appearance in plasma [16,31]. Further important influencing factors are concomitantly applied: anticholinergic antiparkinsonian drugs, alterations of the large neutral amino acid gastrointestinal transport system and gastric emptying velocity [16,17,29,31]. In contrast to the conventional levodopa preparations, pharmacokinetic behaviour of levodopa of soluble levodopa formulations is more independent of gastric emptying speed.…”

Arzneimittelinteraktionen bei der Antiparkinson-Therapie

“…Alpha-Dihydroergocryptin (α-DHEC) beeinträchtigt die Bioverfügbarkeit von Levodopa so geringfügig, dass eine Dosiskorrektur in der Praxis nicht notwendig ist (30). Warfarin verändert die Pergolid-Proteinbindung mit der Folge der Steigerung von Dyskinesien.…”

Bioequivalence of a Novel High-dose Oral Formulation of α-Dihydroergocryptine

“…Im Gegensatz dazu wurden relativ geringe intraindividuelle Unterschiede zwischen den beiden Behandlungen festgestellt: Für das Tag-Profil nach der morgendlichen Dosis betrugen die geschätzten Quotienten der wahren Mittelwerte (µ T :µ R ) für C max , C min und C av jeweils 1.18 (90% CI: 0.96 bis 1.43 − CV m : peak and total exposure were about two times higher than in normal controls with normal renal function [5,6]. There is no clinically relevant pharmacokinetic effect of DHEC on the pharmacokinetics of concomitantly administered levodopa [7] and digoxin [8].…”