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Concentration‐effect relationship of levodopa in patients with Parkinson's disease after oral administration of an immediate release and a controlled release formulation.
Author(s) -
Harder S,
Baas H,
Bergemann N,
Demisch L,
Rietbrock S
Publication year - 1995
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1995.tb04407.x
Subject(s) - levodopa , cmax , benserazide , pharmacokinetics , pharmacodynamics , oral administration , medicine , pharmacology , parkinson's disease , disease
1. The relationship between plasma concentration of levodopa and motor‐ response was investigated in 12 patients with Parkinson's disease who showed marked response fluctuations, after a single oral dose of an immediate release (IR) formulation (100 mg levodopa/25 mg genserazide) and a controlled release (CR) formulation (300 mg levodopa/75 mg benserazide), using a double‐blind, randomized, cross‐over design. 2. The sum score of the Columbia University Rating Scale (CURS sigma) was used for pharmacodynamic assessment. A sigmoidal Emax‐model was fitted to the data using a semiparametric pharmacokinetic/dynamic approach. 3. The dose‐corrected AUC of levodopa after the IR‐formulation was 27.5 (+/‐ 9.1 s.d.) ng ml‐1 h per mg and 23.2 (+/‐ 4.6 s.d.) ng ml‐1 h per mg after the CR‐formulation. Cmax was 1714 (+/‐ 1027 s.d.) ng ml‐1 after the IR‐formulation and 1494 (+/‐ 383 s.d.) ng ml‐1 after the CR‐ formulation. 4. With both preparations, the maximal response to levodopa (Emax) was a decrease in the CURS sigma rating of about 27 scores. Estimates of the EC50 of levodopa were 495 (+/‐ 144 s.d.) ng ml‐ 1 (IR) and 1024 (+/‐ 502 s.d.) ng ml‐1 (CR), respectively (95%‐CI: 1.51‐ 2.66, point estimator 1.95). The mean duration of the motor response was 1.9 (+/‐ 0.5 s.d.) h (IR) and 2.8 (+/‐ 0.7 s.d.) h (CR), respectively (95%‐CI: 1.12‐2.04, point estimator 1.53).(ABSTRACT TRUNCATED AT 250 WORDS)