Clinical and pharmacokinetic comparison of oral and duodenal delivery of levodopa/carbidopa in patients with Parkinson's disease with a fluctuating response to levodopa

Abstract

The clinical effects and pharmacokinetics of orally and intraduodenally administered levodopa, in four patients with Parkinson's disease have been compared. The patients had unpredictable fluctuations in motor function and episodic unresponsiveness to single doses of levodopa. The pharmacokinetic and clinical data of these patients were compared retrospectively with those of Parkinsonian patients with fluctuations in motor performance but with preserved clinical responses to single oral doses of levodopa. There was a threshold plasma concentration of levodopa associated with the "switch on or off" effect. In addition, rapid attainment of this critical plasma concentration was associated with a quicker onset of action and a more prolonged clinical response. All the patients had delayed absorption of levodopa related to delayed and erratic gastric emptying, which contributed to the fluctuation in motor response. In contrast, the patients with fluctuating motor effects but a preserved clinical response after levodopa showed an absorption pattern comparable to that of four patients studied after duodenal delivery of levodopa. It is suggested that there is a subgroup of patients with fluctuating responses due mainly to altered peripheral pharmacokinetics of levodopa. The findings demonstrate the relevance of routine measurements of plasma levodopa in patients with Parkinson's disease in whom there are fluctuations in motor performance.