title: Pharmacokinetics of levodopa, carbidopa, and 3-O-methyldopa following 16-hour jejunal infusion of levodopa-carbidopa intestinal gel in advanced Parkinson's disease patients.
abstract: Motor complications of Parkinson's disease (PD) are a consequence of pulsatile dopaminergic stimulation from standard oral levodopa therapy. Levodopa-carbidopa intestinal gel (LCIG) is infused continuously via an intrajejunal percutaneous gastrostomy tube. This was the first study designed to characterize the full pharmacokinetic profiles of levodopa, carbidopa, and levodopa metabolite, 3-O-methyldopa (3-OMD) with 16-h LCIG infusion. Nineteen advanced PD patients (mean age, 65 years) who were on LCIG therapy for ≥30 days were enrolled. Patients received their individualized LCIG infusion doses, and serial pharmacokinetic samples were collected. Eighteen patients completed the study; 19 were assessed for safety. Mean (SD) total levodopa and carbidopa doses were 1,580 (403) and 395 (101) mg, respectively. Mean (SD) C(avg) (μg/mL) were 2.9 (0.84) for levodopa, 17.1 (4.99) for 3-OMD, and 0.22 (0.08) for carbidopa. The degree of fluctuation [defined as (C(max)-C(min))/C(avg)] in levodopa, 3-OMD, and carbidopa plasma concentrations was very low (0.52, 0.21, and 0.96, respectively) during hours 2-16 of infusion. Accordingly, the within-subject coefficients of variation in levodopa, 3-OMD, and carbidopa concentrations were low (13%, 6%, and 19%, respectively). Three patients (16%) reported ≥1 treatment-emergent adverse event; none were considered severe. Continuous intrajejunal LCIG infusion maintained stable plasma levodopa levels over 16 h. Consistent exposure has been shown to reduce motor and nonmotor complications associated with oral medications. LCIG was well tolerated, consistent with previous reports.
authors.affiliation: Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
authors.forename: Dag
authors.initials: D
authors.lastname: Nyholm
authors.forename: Per
authors.initials: P
authors.lastname: Odin
authors.forename: Anders
authors.initials: A
authors.lastname: Johansson
authors.forename: Krai
authors.initials: K
authors.lastname: Chatamra
authors.forename: Charles
authors.initials: C
authors.lastname: Locke
authors.forename: Sandeep
authors.initials: S
authors.lastname: Dutta
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Othman
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001711:Biotransformation; D002230:Carbidopa / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D004338:Drug Combinations; D005260:Female; D005782:Gels; D005858:Germany; D006801:Humans; D007260:Infusion Pumps; D007408:Intestinal Absorption; D007441:Intubation, Gastrointestinal / Q000295:instrumentation; D007583:Jejunum / Q000378:metabolism*; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D013548:Sweden; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000978:Antiparkinson Agents; D004338:Drug Combinations; D005782:Gels; C009265:carbidopa, levodopa drug combination; D014443:Tyrosine; D007980:Levodopa; D002230:Carbidopa; C008404:3-methoxytyrosine