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Pharmacokinetics of Levodopa, Carbidopa, and 3-O-Methyldopa Following 16-hour Jejunal Infusion of Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson's Disease Patients

Nyholm, Dag; Odin, Per LU ; Johansson, Anders; Chatamra, Krai; Locke, Charles; Dutta, Sandeep and Othman, Ahmed A. (2013) In AAPS Journal 15(2). p.316-323
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 a parts per thousand yen30 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... (More)
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 a parts per thousand yen30 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) (mu g/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) -aEuro parts per thousand 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 a parts per thousand yen1 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Duodopa, LCIG, Levodopa-carbidopa intestinal gel, Parkinson's disease, Pharmacokinetics
in
AAPS Journal
volume
15
issue
2
pages
316 - 323
publisher
American Association of Pharmaceutical Scientists
external identifiers
  • wos:000317136100003
  • scopus:84877037039
ISSN
1550-7416
DOI
10.1208/s12248-012-9439-1
language
English
LU publication?
yes
id
cb798894-ebab-411c-a49a-ef68b080bc62 (old id 3854750)
date added to LUP
2013-07-01 07:04:00
date last changed
2019-09-17 02:54:50
@article{cb798894-ebab-411c-a49a-ef68b080bc62,
  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 a parts per thousand yen30 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) (mu g/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) -aEuro parts per thousand 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 a parts per thousand yen1 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.},
  author       = {Nyholm, Dag and Odin, Per and Johansson, Anders and Chatamra, Krai and Locke, Charles and Dutta, Sandeep and Othman, Ahmed A.},
  issn         = {1550-7416},
  keyword      = {Duodopa,LCIG,Levodopa-carbidopa intestinal gel,Parkinson's disease,Pharmacokinetics},
  language     = {eng},
  number       = {2},
  pages        = {316--323},
  publisher    = {American Association of Pharmaceutical Scientists},
  series       = {AAPS Journal},
  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},
  url          = {http://dx.doi.org/10.1208/s12248-012-9439-1},
  volume       = {15},
  year         = {2013},
}