Garcia JJ, Fernandez N, Calle A, Diez MJ, Sahagun A, Sierra M
Effects of Plantago ovata husk on levodopa (with carbidopa) bioavailability in rabbits with autonomic gastrointestinal disorders. [JOURNAL ARTICLE]
Drug Metab Dispos 2009 Apr 23.
Gastrointestinal dysfunction is common in Parkinson's disease. Fiber therapy could be used to reduce the symptoms of gastrointestinal motility disorders. In a previous study, we showed that slowed gastrointestinal motility modified levodopa pharmacokinetics: AUC and Cmax decreased, and the elimination was delayed. In this study, we evaluated whether or not the hydrosoluble fiber Plantago ovata husk is useful in improving levodopa pharmacokinetics in rabbits with autonomic gastrointestinal disorders induced by the administration of the anticholinergic biperiden. Levodopa+carbidopa (20:5 mg/kg), biperiden (100 microg/kg), and P. ovata husk (at two different doses: 100 and 400 mg/kg) were administered orally to rabbits for two periods of time (7 or 14 days). In all groups of animals, the AUC values were about 50% higher on the final day of treatment than on day one. Cmax was also higher, with the greater increase at the 400 mg/kg dose of fiber, which resulted in a boost of about 35%. On day 1 of treatment, and with both doses of fiber, AUC values were very similar to those obtained in previous work in rabbits with normal gastrointestinal motility, but the Cmax was lower. However, after 7 or 14 days, the AUC values were higher, but Cmax remained lower. The greatest differences were observed in Cmin, obtaining the highest increase with the dose of 400 mg/kg fiber on day 14 of treatment (349.8%). Plantago ovata husk could be beneficial in patients with Parkinson's disease because it regulates stool transit in the intestine and because it improves levodopa pharmacokinetics when gastrointestinal peristalsis is slowed. These changes could lead to a possible delay in the onset of dyskinesias and to changes in prognosis.
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