Population pharmacokinetics of levodopa in subjects with advancedParkinson's disease: levodopa‐carbidopa intestinal gel infusionvs. oral tablets

Content Provider	Scilit
Author	Othman, Ahmed A. Dutta, Sandeep
Copyright Year	2014
Description	Journal: British journal of clinical pharmacology Levodopa-carbidopa intestinal gel (LCIG) provides continuous levodopa-carbidopa delivery through intrajejunal infusion. This study characterized the population pharmacokinetics of levodopa following a 16 h jejunal infusion of LCIG or frequent oral administration of levodopa-carbidopa tablets (LC-oral) in subjects with advanced Parkinson's disease (PD). A non-linear mixed-effects model of levodopa pharmacokinetics was developed using serial plasma concentrations from an LCIG phase 1 study and a phase 3 double-blind, double-dummy study of the efficacy and safety of LCIG compared with LC-oral in advanced PD patients (n = 68 for model development; 45 on LCIG and 23 on LC-oral). The final model was internally evaluated using stochastic simulations and bootstrap and externally evaluated using sparse pharmacokinetic data from 311 subjects treated in a long term safety study of LCIG. The final model was a two compartment model with a transit compartment for absorption, first order elimination, bioavailability for LCIG (97%; confidence interval = 95% to 98%) relative to LC-oral, different first order transit absorption rate constants (LCIG = 9.2 h–1 vs. LC-oral = 2.4 h–1; corresponding mean absorption time of 7 min for LCIG vs. 25 min for LC-oral) and different residual (intra-subject) variability for LCIG (15% proportional error, 0.3 μg ml−1 additive error) vs. LC-oral (29% proportional error, 0.59 μg ml−1 additive error). Estimated oral clearance and steady-state volume of distribution for levodopa were 24.8 l h−1 and 131 l, respectively. LCIG administration results in faster absorption, comparable levodopa bioavailability and significantly reduced intra-subject variability in levodopa concentrations relative to LC-oral administration.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4168384/pdf
e-ISSN	13652125
DOI	10.1111/bcp.12324
Journal	British journal of clinical pharmacology
Issue Number	1
Volume Number	78
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2014-06-20
Access Restriction	Open
Subject Keyword	Journal: British journal of clinical pharmacology Parkinson's Disease Population Pharmacokinetics
Content Type	Text
Resource Type	Article