Jejunal Infusion of levodopa-carbidopa intestinal gel versus oral administration of levodopa-carbidopa tablets in japanese subjects with advanced Parkinson's disease: pharmacokinetics and pilot efficacy and safety.
Clin Pharmacokinet
; 54(9): 975-84, 2015 Sep.
Article
em En
| MEDLINE
| ID: mdl-25875940
ABSTRACT
BACKGROUND AND OBJECTIVE:
Oral levodopa-carbidopa (LC-oral) treatment in advanced Parkinson's disease (PD) is associated with motor complications due to large fluctuations in levodopa plasma concentrations. Levodopa-carbidopa intestinal gel (LCIG) provides individualized continuous levodopa-carbidopa delivery through intrajejunal infusion. This study evaluated the pharmacokinetics, safety, and efficacy of LCIG relative to LC-oral in Japanese subjects with advanced PD.METHODS:
Subjects with advanced PD were converted from their anti-PD medications to individually optimized doses of LC-oral (101 levodopacarbidopa ratio) for 28 days (baseline; period 1) followed by switching to intrajejunal infusion of LCIG (41 ratio) for 21 days (period 2). Pharmacokinetics, adverse events (AEs), and efficacy were assessed.RESULTS:
Eight patients were enrolled. Six received LCIG and four reported at least one AE [most common fall (33.3 %), dyskinesia (33.3 %)]; one discontinued due to an AE. The average daily dose was 1230/123 and 1370/342 mg levodopa/carbidopa for LC-oral and LCIG, respectively, at the end of each period. The degree of fluctuation and intra-subject variability of levodopa plasma concentrations were 5.5- and 4-fold lower, respectively, with LCIG than with LC-oral. Levodopa bioavailability was 99 % for LCIG relative to LC-oral. Compared with baseline, LCIG decreased "Off" time (2.68 h, P = 0.002) and increased "On" time without troublesome dyskinesia (2.35 h, P = 0.006) in the PD Diary(©). With the small sample size, no statistically significant changes were seen on other efficacy endpoints.CONCLUSIONS:
In Japanese subjects with advanced PD, LCIG resulted in an improved pharmacokinetic profile that appeared to be associated with reduced motor complications compared with LC-oral. These results extend previous findings in mainly Caucasian populations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Carbidopa
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Levodopa
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Aged
/
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article