title: 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: 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: Clinical Pharmacology and Pharmacometrics, AbbVie, 1 North Waukegan Road, Building AP13A-3, North Chicago, IL, 60064, USA, ahmed.othman@abbvie.com.
authors: Ahmed A
authors: AA
authors: Othman
authors: Krai
authors: K
authors: Chatamra
authors: Mohamed-Eslam F
authors: ME
authors: Mohamed
authors: Sandeep
authors: S
authors: Dutta
authors: Janet
authors: J
authors: Benesh
authors: Masayoshi
authors: M
authors: Yanagawa
authors: Masahiro
authors: M
authors: Nagai
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002230:Carbidopa / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D005782:Gels; D006801:Humans; D007263:Infusions, Parenteral; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism*; D010865:Pilot Projects; D057285:Precision Medicine; D013607:Tablets
chemical_list: D000978:Antiparkinson Agents; D004338:Drug Combinations; D005782:Gels; D013607:Tablets; D007980:Levodopa; D002230:Carbidopa