THE EFFECTS OF CISAPRIDE ON PLASMA L-DOPA LEVELS AND CLINICAL-RESPONSE IN PARKINSONS-DISEASE

Cisapride (CIS) is a prokinetic agent that increases gastrointestinal motility in normal individuals and improves constipation in Parkinson' s disease (PD). We studied the effects of CIS on the clinical response and the peripheral pharmacokinetics of orally administered L-dopa giv en to patients with PD. Twenty patients with idiopathic PD and chronic constipation, whose response to L-dopa was suboptimal or characterize d by fluctuations, agreed to participate in an open study that lasted for 2 weeks. Fourteen patients completed the study (mean age 65 +/- 9. 3 years, mean duration of treatment 5.7 +/- 4.2 years, mean L-dopa dai ly doses 658.9 +/- 269.9 mg); six patients were excluded due to lack o f compliance or changes in medication during the study. The end points of the study included the mean levels of L-dopa, the height of the pe ak of L-dopa in plasma, mean plasma levels of 3-OM-dopa, and the speed and quality of gait and visuomanual coordination before and during tr eatment with CIS. CIS increased peak plasma levels of L-dopa by 37% an d the mean plasma levels of L-dopa by 13% with respect to those obtain ed with the same dose of L-dopa before the addition of CIS. Therefore, CIS appears to increase early absorption of L-dopa through accelerati on of gastric emptying. CIS also increased plasma 3-OM-dopa levels, im proved visuomanual coordination, and reduced gait disability. CIS impr oves gastrointestinal function and response to L-dopa in patients with PD and could be a helpful add-on medication in these patients.