[Slow-release L-dopa vs. standard L-dopa in Parkinson patients in various stages of the disease. Studies of pharmacokinetics and motor effectiveness].
[Slow-release L-dopa vs. standard L-dopa in Parkinson patients in various stages of the disease. Studies of pharmacokinetics and motor effectiveness].
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Original abstract
Most strategies for the therapeutic management of L-dopa-dependent fluctuations in Parkinsonian patients aim at the continuous stimulation of postsynaptic dopaminergic receptors. Slow release- (s.r.-) preparations of L-dopa appear to present a promising and effective solution for this objective. Clinical experience with the available s.-r.-preparations has lead to the identification of some specific areas for their use. It has not been possible, however, to sharply define their entire range of application. The present study, therefore, compared single dose kinetics and pharmacodynamic effects of three dosages of L-dopa/bensearazid-s.r.-preparation (ASTA H995 125 mg, 250 mg, 275 mg) in a controlled, randomised, 4-fold, double blind, cross over design. The effects were studied in 12 Parkinsonian patients with vs. without motor fluctuations. Motor responses were monitored multimodally (according to the Columbia University Rating Scale, the Purdue Pegboard, and a modified version of the Webster Step Second Test). The pharmacokinetic effectiveness of the s.r.-approach could be demonstrated in both groups. It was possible to ascertain significant differences in kinetics between the various L-dopa-s.r.-dosages and L-dopa standard. No significant difference, however, appeared in the pharmacokinetic characteristic values (Cmax, Tmax, AUC0-->infinity, T1/2) between the fluctuating and non-fluctuating patients. A circumscribed motor effect was demonstrable only for those patients with fluctuations. As expected, motor responses were delayed and lasted longer in these patients after applying the L-dopa-s.r.-dosage. A three times greater dosage of L-dopa-s.r. was required in order to obtain a superior motor effect to the L-dopa-standard-preparation.(ABSTRACT TRUNCATED AT 250 WORDS)