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.

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 (10:1 levodopa:carbidopa ratio) for 28 days (baseline; period 1) followed by switching to intrajejunal infusion of LCIG (4:1 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.

• Authors: Ahmed A Othman, Krai Chatamra, Mohamed-Eslam F Mohamed, Sandeep Dutta, Janet Benesh, Masayoshi Yanagawa, Masahiro Nagai
• Journal: Clinical pharmacokinetics (Clin Pharmacokinet) Vol. 54 Issue 9 Pg. 975-84 (Sep 2015) ISSN: 1179-1926 [Electronic] Switzerland
• PMID: 25875940 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiparkinson Agents
• Drug Combinations
• Gels
• Tablets
• Levodopa
• Carbidopa

Topics

• Administration, Oral
• Aged
• Antiparkinson Agents (administration & dosage, adverse effects, pharmacokinetics)
• Carbidopa (administration & dosage, adverse effects, pharmacokinetics)
• Drug Combinations
• Female
• Gels
• Humans
• Infusions, Parenteral
• Levodopa (administration & dosage, adverse effects, pharmacokinetics)
• Male
• Middle Aged
• Parkinson Disease (drug therapy, metabolism)
• Pilot Projects
• Precision Medicine
• Tablets