PMID- 25875940
OWN - NLM
STAT- MEDLINE
DCOM- 20160517
LR  - 20220316
IS  - 1179-1926 (Electronic)
IS  - 0312-5963 (Print)
IS  - 0312-5963 (Linking)
VI  - 54
IP  - 9
DP  - 2015 Sep
TI  - 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.
PG  - 975-84
LID - 10.1007/s40262-015-0265-3 [doi]
AB  - 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((c)). 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.
FAU - Othman, Ahmed A
AU  - Othman AA
AD  - Clinical Pharmacology and Pharmacometrics, AbbVie, 1 North Waukegan Road, 
      Building AP13A-3, North Chicago, IL, 60064, USA, ahmed.othman@abbvie.com.
FAU - Chatamra, Krai
AU  - Chatamra K
FAU - Mohamed, Mohamed-Eslam F
AU  - Mohamed ME
FAU - Dutta, Sandeep
AU  - Dutta S
FAU - Benesh, Janet
AU  - Benesh J
FAU - Yanagawa, Masayoshi
AU  - Yanagawa M
FAU - Nagai, Masahiro
AU  - Nagai M
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Clin Pharmacokinet
JT  - Clinical pharmacokinetics
JID - 7606849
RN  - 0 (Antiparkinson Agents)
RN  - 0 (Drug Combinations)
RN  - 0 (Gels)
RN  - 0 (Tablets)
RN  - 46627O600J (Levodopa)
RN  - MNX7R8C5VO (Carbidopa)
SB  - IM
MH  - Administration, Oral
MH  - Aged
MH  - Antiparkinson Agents/administration & dosage/adverse effects/pharmacokinetics
MH  - Carbidopa/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Drug Combinations
MH  - Female
MH  - Gels
MH  - Humans
MH  - Infusions, Parenteral
MH  - Levodopa/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Male
MH  - Middle Aged
MH  - Parkinson Disease/*drug therapy/*metabolism
MH  - Pilot Projects
MH  - Precision Medicine
MH  - Tablets
PMC - PMC4559582
EDAT- 2015/04/16 06:00
MHDA- 2016/05/18 06:00
PMCR- 2015/04/15
CRDT- 2015/04/16 06:00
PHST- 2015/04/16 06:00 [entrez]
PHST- 2015/04/16 06:00 [pubmed]
PHST- 2016/05/18 06:00 [medline]
PHST- 2015/04/15 00:00 [pmc-release]
AID - 265 [pii]
AID - 10.1007/s40262-015-0265-3 [doi]
PST - ppublish
SO  - Clin Pharmacokinet. 2015 Sep;54(9):975-84. doi: 10.1007/s40262-015-0265-3.