Effects of slowed gastrointestinal motility on levodopa pharmacokinetics

Abstract

Autonomic disorders are often seen in Parkinson's disease, with disturbances of the gastrointestinal tract occurring most frequently. These disorders, mainly a delay in gastric emptying and slowed gastrointestinal motility, can modify the pharmacokinetics and effectiveness of drugs used to treat Parkinson's disease and administered orally. In this study, we evaluated in a rabbit model the pharmacokinetics of levodopa (administered with carbidopa) in the context of gastrointestinal motility slowed by the administration of an anticholinergic drug. Levodopa+carbidopa (20:5 mg/kg) and the anticholinergic biperiden (100 μg/kg) were orally administered to rabbits over one of two time periods (7 or 14 days) to verify the stabilization of levodopa concentrations. The values of the area under the curve (AUC) and Cmax were higher on the final day of treatment with an increase in AUC of 25% on day 7 and 33.4% on day 14; for Cmax, the increase was 15% on day 7 and 12.8% on day 14. The values of AUC and Cmax were lower than those obtained when levodopa was administered to rabbits with normal gastrointestinal motility. The values obtained for Cmin (baseline sample obtained before administration) also increased with treatment duration (24% and 47.4% on days 7 and 14, respectively). These values were higher than those obtained in the absence of anticholinergic administration. We conclude that, under our experimental conditions of slowed gastrointestinal motility, levodopa absorption diminishes, and final concentrations and Cmin are higher than under conditions of normal motility.