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Effects of slowed gastrointestinal motility on levodopa pharmacokinetics
Autor
Facultad/Centro
Área de conocimiento
Datos de la obra
Autonomic Neuroscience: Basic and Clinical, 2010, n. 156
Editor
Elsevier
Fecha
2010-03-23
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.
Materia
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Peer review
SI
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