PT  - JOURNAL ARTICLE
AU  - Juan J. García
AU  - Nélida Fernández
AU  - Ángela P. Calle
AU  - M. José Diez
AU  - Ana Sahagún
AU  - Matilde Sierra
TI  - Effects of <em>Plantago ovata</em> Husk on Levodopa (with Carbidopa) Bioavailability in Rabbits with Autonomic Gastrointestinal Disorders
AID  - 10.1124/dmd.108.026229
DP  - 2009 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 1434--1442
VI  - 37
IP  - 7
4099  - http://dmd.aspetjournals.org/content/37/7/1434.short
4100  - http://dmd.aspetjournals.org/content/37/7/1434.full
SO  - Drug Metab Dispos2009 Jul 01; 37
AB  - 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: area under the plasma concentration-time curve (AUC) and maximum plasma concentration (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 μg/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 approximately 50% higher on the final day of treatment than on day 1. Cmax was also higher, with the greater increase at the 400 mg/kg dose of fiber, which resulted in a boost of approximately 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 plasma concentration before drug administration (Cmin), for which the highest increase was obtained with the dose of 400 mg/kg fiber on day 14 of treatment (349.8%). P. 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.