American Society for Pharmacology and Experimental Therapeutics
Abstract
P. 1434-1442Gastrointestinal 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 g/
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.S