The Experts below are selected from a list of 9105 Experts worldwide ranked by ideXlab platform
Robert A. Hauser - One of the best experts on this subject based on the ideXlab platform.
-
Extended-release Carbidopa-levodopa (IPX066) compared with immediate-release Carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations: a phase 3 randomised, double-blind trial
The Lancet. Neurology, 2013Co-Authors: Robert A. Hauser, Ann Hsu, Sherron Kell, Alberto J. Espay, Kapil D. Sethi, Mark Stacy, William G. Ondo, Martin O'connell, Suneel GuptaAbstract:Summary Background IPX066 is an oral, extended-release, capsule formulation of Carbidopa-levodopa. We aimed to assess this extended-release formulation versus immediate-release Carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations. Methods We did a phase 3, randomised, double-blind, double-dummy study at 68 academic and clinical centres in North America and Europe. Patients with Parkinson's disease who had at least 2·5 h per day of off-time underwent 3 weeks of open-label immediate-release Carbidopa-levodopa dose adjustment followed by 6 weeks of open-label extended-release Carbidopa-levodopa dose conversion. These patients were then randomly allocated (1:1), by use of an interactive web-response system, to 13 weeks of double-blind treatment with extended-release or immediate-release Carbidopa-levodopa plus matched placebos. The primary efficacy measure was off-time as a percentage of waking hours in all patients randomly allocated to treatment groups, adjusted for baseline value. This study is registered with ClinicalTrials.gov, number NCT00974974. Findings Between Sept 29, 2009, and Aug 16, 2010, we enrolled 471 participants, of whom 393 (83%) were randomly allocated in the double-blind maintenance period and were included in the main efficacy analyses. As a percentage of waking hours, 201 patients treated double-blind with extended-release Carbidopa-levodopa (mean 3·6 doses per day [SD 0·7]) had greater reductions in off-time than did 192 patients treated double-blind with immediate-release Carbidopa-levodopa (mean 5·0 doses per day [1·2]). Covariate-adjusted end-of-study means were 23·82% (SD 14·91) for extended-release Carbidopa-levodopa and 29·79% (15·81) for immediate-release Carbidopa-levodopa (mean difference −5·97, 95% CI −9·05 to −2·89; p vs two [1%] of 192 patients allocated immediate-release Carbidopa-levodopa), nausea (six [3%] vs three [2%]), and falls (six [3%] vs four [2%]). Interpretation Extended-release Carbidopa-levodopa might be a useful treatment for patients with Parkinson's disease who have motor fluctuations, with potential benefits including decreased off-time and reduced levodopa dosing frequency. Funding Impax Laboratories.
-
Levodopa/Carbidopa/entacapone for the treatment of Parkinson's disease
Aging Health, 2006Co-Authors: Johan Samanta, Robert A. HauserAbstract:The triple combination levodopa/Carbidopa/entacapone tablet provides the clinical benefits of adding entacapone therapy to Carbidopa/levodopa while affording the convenience of fewer pills. Entacapone is a catechol-O-methyl transferase inhibitor that slows the peripheral metabolism of levodopa, thereby increasing its central bioavailability. Clinically, the addition of entacapone to levodopa/Carbidopa in Parkinson's disease patients with wearing-off fluctuations increases ‘on’ time, improves motor function and activities of daily living, and allows for a reduction of the levodopa dose. Levodopa/Carbidopa/entacapone is indicated for use in patients with idiopathic Parkinson's disease who are being treated with immediate-release levodopa and experiencing the signs and symptoms of end-of-dose wearing-off. Clinical trial data in levodopa-treated Parkinson's disease patients who are not experiencing wearing-off demonstrate that the addition of entacapone is associated with a mild but significant improvement in...
-
levodopa Carbidopa entacapone stalevo
Neurology, 2004Co-Authors: Robert A. HauserAbstract:A levodopa/Carbidopa/entacapone combination product (Stalevo) was recently approved to treat patients with idiopathic Parkinson’s disease (PD) who experience end-of-dose “wearing-off.” Stalevo is available in dose combinations of levodopa/Carbidopa/entacapone 50/12.5/200 mg (Stalevo 50), 100/25/200 mg (Stalevo 100), and 150/37.5/200 mg (Stalevo 150). A series of pharmacokinetic studies demonstrated bioequivalence between Stalevo and corresponding dosages of levodopa/Carbidopa plus entacapone. A clinical advantage of Stalevo is that patients can take one pill rather than two (or more) separate tablets. In addition, Stalevo 50 and 100 tablets are smaller than entacapone tablets. These advantages may be particularly beneficial for patients taking many pills, those who have difficulty following complex medication regimens, and those with swallowing difficulty. Most PD patients taking levodopa/Carbidopa immediate-release (IR) plus entacapone can be directly switched to the corresponding dose Stalevo product. For fluctuating PD patients taking levodopa/Carbidopa IR without entacapone, switching to the corresponding Stalevo tablet is analogous to adding entacapone. In switching patients who are receiving levodopa/Carbidopa controlled-release (CR), it should be noted that the bioavailability of levodopa from levodopa/Carbidopa CR is approximately 70–75% that of levodopa/Carbidopa IR products, including Stalevo.
-
Levodopa/Carbidopa/entacapone (Stalevo).
Neurology, 2004Co-Authors: Robert A. HauserAbstract:A levodopa/Carbidopa/entacapone combination product (Stalevo) was recently approved to treat patients with idiopathic Parkinson’s disease (PD) who experience end-of-dose “wearing-off.” Stalevo is available in dose combinations of levodopa/Carbidopa/entacapone 50/12.5/200 mg (Stalevo 50), 100/25/200 mg (Stalevo 100), and 150/37.5/200 mg (Stalevo 150). A series of pharmacokinetic studies demonstrated bioequivalence between Stalevo and corresponding dosages of levodopa/Carbidopa plus entacapone. A clinical advantage of Stalevo is that patients can take one pill rather than two (or more) separate tablets. In addition, Stalevo 50 and 100 tablets are smaller than entacapone tablets. These advantages may be particularly beneficial for patients taking many pills, those who have difficulty following complex medication regimens, and those with swallowing difficulty. Most PD patients taking levodopa/Carbidopa immediate-release (IR) plus entacapone can be directly switched to the corresponding dose Stalevo product. For fluctuating PD patients taking levodopa/Carbidopa IR without entacapone, switching to the corresponding Stalevo tablet is analogous to adding entacapone. In switching patients who are receiving levodopa/Carbidopa controlled-release (CR), it should be noted that the bioavailability of levodopa from levodopa/Carbidopa CR is approximately 70–75% that of levodopa/Carbidopa IR products, including Stalevo.
Suneel Gupta - One of the best experts on this subject based on the ideXlab platform.
-
Pharmacokinetics of Rytary^®, An Extended-Release Capsule Formulation of Carbidopa–Levodopa
Clinical Pharmacokinetics, 2017Co-Authors: Aravind Mittur, Suneel Gupta, Nishit B. ModiAbstract:Parkinson’s disease (PD) is a chronic progressive neurological disorder characterized by resting tremor, rigidity, bradykinesia, gait disturbance, and postural instability. Levodopa, the precursor to dopamine, coadministered with Carbidopa or benserazide, aromatic amino acid decarboxylase inhibitors, is the most effective and widely used therapeutic agent in the treatment of PD. With continued levodopa treatment, a majority of patients develop motor complications such as dyskinesia and motor ‘on-off’ fluctuations, which are, in part, related to the fluctuations in plasma concentrations of levodopa. A new extended-release (ER) Carbidopa–levodopa capsule product (also referred to as IPX066) was developed and approved in the US as Rytary^® and in the EU as Numient^®. The capsule formulation is designed to provide an initial rapid absorption of levodopa comparable to immediate-release (IR) Carbidopa–levodopa, and to subsequently provide stable levodopa concentrations with reduced peak-to-trough excursions in plasma concentrations in order to reduce motor fluctuations associated with pulsatile stimulation of dopamine receptors and to minimize dyskinesia. Phase III studies of this ER Carbidopa–levodopa capsule formulation in patients with PD have shown a significant reduction in ‘off’ time compared with IR Carbidopa–levodopa and Carbidopa–levodopa–entacapone. We present a review of the clinical pharmacokinetics and pharmacodynamics of this ER product of Carbidopa–levodopa in healthy subjects and in patients with PD.
-
Pharmacokinetics of Rytary ® , An Extended-Release Capsule Formulation of Carbidopa–Levodopa
Clinical pharmacokinetics, 2017Co-Authors: Aravind Mittur, Suneel Gupta, Nishit B. ModiAbstract:Parkinson’s disease (PD) is a chronic progressive neurological disorder characterized by resting tremor, rigidity, bradykinesia, gait disturbance, and postural instability. Levodopa, the precursor to dopamine, coadministered with Carbidopa or benserazide, aromatic amino acid decarboxylase inhibitors, is the most effective and widely used therapeutic agent in the treatment of PD. With continued levodopa treatment, a majority of patients develop motor complications such as dyskinesia and motor ‘on-off’ fluctuations, which are, in part, related to the fluctuations in plasma concentrations of levodopa. A new extended-release (ER) Carbidopa–levodopa capsule product (also referred to as IPX066) was developed and approved in the US as Rytary® and in the EU as Numient®. The capsule formulation is designed to provide an initial rapid absorption of levodopa comparable to immediate-release (IR) Carbidopa–levodopa, and to subsequently provide stable levodopa concentrations with reduced peak-to-trough excursions in plasma concentrations in order to reduce motor fluctuations associated with pulsatile stimulation of dopamine receptors and to minimize dyskinesia. Phase III studies of this ER Carbidopa–levodopa capsule formulation in patients with PD have shown a significant reduction in ‘off’ time compared with IR Carbidopa–levodopa and Carbidopa–levodopa–entacapone. We present a review of the clinical pharmacokinetics and pharmacodynamics of this ER product of Carbidopa–levodopa in healthy subjects and in patients with PD.
-
Extended-release Carbidopa-levodopa (IPX066) compared with immediate-release Carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations: a phase 3 randomised, double-blind trial
The Lancet. Neurology, 2013Co-Authors: Robert A. Hauser, Ann Hsu, Sherron Kell, Alberto J. Espay, Kapil D. Sethi, Mark Stacy, William G. Ondo, Martin O'connell, Suneel GuptaAbstract:Summary Background IPX066 is an oral, extended-release, capsule formulation of Carbidopa-levodopa. We aimed to assess this extended-release formulation versus immediate-release Carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations. Methods We did a phase 3, randomised, double-blind, double-dummy study at 68 academic and clinical centres in North America and Europe. Patients with Parkinson's disease who had at least 2·5 h per day of off-time underwent 3 weeks of open-label immediate-release Carbidopa-levodopa dose adjustment followed by 6 weeks of open-label extended-release Carbidopa-levodopa dose conversion. These patients were then randomly allocated (1:1), by use of an interactive web-response system, to 13 weeks of double-blind treatment with extended-release or immediate-release Carbidopa-levodopa plus matched placebos. The primary efficacy measure was off-time as a percentage of waking hours in all patients randomly allocated to treatment groups, adjusted for baseline value. This study is registered with ClinicalTrials.gov, number NCT00974974. Findings Between Sept 29, 2009, and Aug 16, 2010, we enrolled 471 participants, of whom 393 (83%) were randomly allocated in the double-blind maintenance period and were included in the main efficacy analyses. As a percentage of waking hours, 201 patients treated double-blind with extended-release Carbidopa-levodopa (mean 3·6 doses per day [SD 0·7]) had greater reductions in off-time than did 192 patients treated double-blind with immediate-release Carbidopa-levodopa (mean 5·0 doses per day [1·2]). Covariate-adjusted end-of-study means were 23·82% (SD 14·91) for extended-release Carbidopa-levodopa and 29·79% (15·81) for immediate-release Carbidopa-levodopa (mean difference −5·97, 95% CI −9·05 to −2·89; p vs two [1%] of 192 patients allocated immediate-release Carbidopa-levodopa), nausea (six [3%] vs three [2%]), and falls (six [3%] vs four [2%]). Interpretation Extended-release Carbidopa-levodopa might be a useful treatment for patients with Parkinson's disease who have motor fluctuations, with potential benefits including decreased off-time and reduced levodopa dosing frequency. Funding Impax Laboratories.
Ahmed A Othman - One of the best experts on this subject based on the ideXlab platform.
-
Levodopa-Carbidopa Intestinal Gel Pharmacokinetics: Lower Variability than Oral Levodopa-Carbidopa.
Journal of Parkinson's disease, 2017Co-Authors: Ahmed A Othman, Krai Chatamra, Charles Locke, Matthew Rosebraugh, Sandeep DuttaAbstract:In a double-blind, double-dummy, double-titration Phase 3 trial in advanced Parkinson’s disease (PD) patients, the efficacy and safety of Levodopa-Carbidopa intestinal gel (LCIG) infusion were characterized relative to immediate-release oral levodopa-Carbidopa (LC-oral) treatment. We present in this report the comparative pharmacokinetic profiles of LCIG and LC-oral from this pivotal study. The results presented in this report clearly demonstrate that LCIG results in lower variability and fluctuations in levodopa and Carbidopa plasma concentrations compared to LC-oral. The superior pharmacokinetic profiles with LCIG were consistent with its improved efficacy compared to LC-oral as demonstrated in this study.
-
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
Clinical Pharmacokinectics, 2015Co-Authors: Ahmed A Othman, Sandeep Dutta, Krai Chatamra, Janet Benesh, Mohamed-eslam F. Mohamed, Masayoshi Yanagawa, Masahiro NagaiAbstract: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.
-
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
Clinical pharmacokinetics, 2015Co-Authors: Ahmed A Othman, Sandeep Dutta, Krai Chatamra, Janet Benesh, Mohamed-eslam F. Mohamed, Masayoshi Yanagawa, Masahiro NagaiAbstract: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.
-
population pharmacokinetics of levodopa in subjects with advanced parkinson s disease levodopa Carbidopa intestinal gel infusion vs oral tablets
British Journal of Clinical Pharmacology, 2014Co-Authors: Ahmed A Othman, Sandeep DuttaAbstract:Aims 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).
-
Pharmacokinetics of Levodopa, Carbidopa, and 3-O-Methyldopa Following 16-hour Jejunal Infusion of Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson's Disease Patients
The AAPS journal, 2012Co-Authors: Dag Nyholm, Sandeep Dutta, Krai Chatamra, Per Odin, Anders Johansson, Charles Locke, Ahmed A OthmanAbstract: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) Cavg (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 (Cmax − Cmin)/Cavg] 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.
Sandeep Dutta - One of the best experts on this subject based on the ideXlab platform.
-
Levodopa-Carbidopa Intestinal Gel Pharmacokinetics: Lower Variability than Oral Levodopa-Carbidopa.
Journal of Parkinson's disease, 2017Co-Authors: Ahmed A Othman, Krai Chatamra, Charles Locke, Matthew Rosebraugh, Sandeep DuttaAbstract:In a double-blind, double-dummy, double-titration Phase 3 trial in advanced Parkinson’s disease (PD) patients, the efficacy and safety of Levodopa-Carbidopa intestinal gel (LCIG) infusion were characterized relative to immediate-release oral levodopa-Carbidopa (LC-oral) treatment. We present in this report the comparative pharmacokinetic profiles of LCIG and LC-oral from this pivotal study. The results presented in this report clearly demonstrate that LCIG results in lower variability and fluctuations in levodopa and Carbidopa plasma concentrations compared to LC-oral. The superior pharmacokinetic profiles with LCIG were consistent with its improved efficacy compared to LC-oral as demonstrated in this study.
-
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
Clinical Pharmacokinectics, 2015Co-Authors: Ahmed A Othman, Sandeep Dutta, Krai Chatamra, Janet Benesh, Mohamed-eslam F. Mohamed, Masayoshi Yanagawa, Masahiro NagaiAbstract: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.
-
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
Clinical pharmacokinetics, 2015Co-Authors: Ahmed A Othman, Sandeep Dutta, Krai Chatamra, Janet Benesh, Mohamed-eslam F. Mohamed, Masayoshi Yanagawa, Masahiro NagaiAbstract: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.
-
population pharmacokinetics of levodopa in subjects with advanced parkinson s disease levodopa Carbidopa intestinal gel infusion vs oral tablets
British Journal of Clinical Pharmacology, 2014Co-Authors: Ahmed A Othman, Sandeep DuttaAbstract:Aims 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).
-
Pharmacokinetics of Levodopa, Carbidopa, and 3-O-Methyldopa Following 16-hour Jejunal Infusion of Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson's Disease Patients
The AAPS journal, 2012Co-Authors: Dag Nyholm, Sandeep Dutta, Krai Chatamra, Per Odin, Anders Johansson, Charles Locke, Ahmed A OthmanAbstract: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) Cavg (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 (Cmax − Cmin)/Cavg] 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.
Sten-magnus Aquilonius - One of the best experts on this subject based on the ideXlab platform.
-
pharmacokinetics of levodopa Carbidopa microtablets versus levodopa benserazide and levodopa Carbidopa in healthy volunteers
Clinical Neuropharmacology, 2012Co-Authors: Dag Nyholm, Tommy Lewander, Tobias Bäckström, Georgios Panagiotidis, Mats Ehrnebo, Christer Nyström, Cecilia Gomestrolin, Sten-magnus AquiloniusAbstract:OBJECTIVES: To compare bioavailability and pharmacokinetics of single doses of 3 different levodopa formulations given orally in healthy volunteers. Two marketed formulations, standard levodopa/Carbidopa, 100/25 mg (LC-100), and dispersible levodopa/benserazide, 100/25 mg (LB-100), were used as reference formulations for a newly developed dispersible microtablet formulation of levodopa/Carbidopa, 5/1.25 mg (LC-5). The microtablets are intended for individualized dosing of levodopa/Carbidopa in Parkinson disease by means of an electronic dose dispenser with a built-in diary for symptom registration. METHODS: A single-dose, open, randomized, 3-way crossover study was performed in 19 healthy subjects. Concentrations of levodopa, Carbidopa, and the metabolite 3-O-MD in plasma were determined after intake of 100 mg of levodopa, that is, one tablet of reference formulations and 20 microtablets of the new formulation. RESULTS: The LC-5 microtablets were bioequivalent to the LC-100 tablets in area under the curve (AUC) and maximum concentration in plasma (Cmax) for levodopa, and to the LB-100 tablets in AUC. The dispersible levodopa/benserazide formulation showed earlier time to Cmax and significantly higher Cmax for levodopa in plasma compared to the microtablets. Carbidopa showed larger interindividual variation in AUC and Cmax than levodopa, and the bioequivalence comparison LC-5/LC-100 for this compound did not reach the target. Nevertheless, comparison of 3-O-MD levels for LC-5/LC-100, assuming proportionality to levodopa levels, demonstrated bioequivalence. CONCLUSIONS: The new levodopa/Carbidopa microtablets had a pharmacokinetic profile that would allow for a convenient switch of therapy from standard tablets. Frequent dose administration of levodopa/Carbidopa microtablets with an electronic dose dispenser might offer an optimal oral drug delivery in Parkinson disease.
-
Pharmacokinetics of levodopa/Carbidopa microtablets versus levodopa/benserazide and levodopa/Carbidopa in healthy volunteers.
Clinical neuropharmacology, 2012Co-Authors: Dag Nyholm, Tommy Lewander, Cecilia Gomes-trolin, Tobias Bäckström, Georgios Panagiotidis, Mats Ehrnebo, Christer Nyström, Sten-magnus AquiloniusAbstract:OBJECTIVES: To compare bioavailability and pharmacokinetics of single doses of 3 different levodopa formulations given orally in healthy volunteers. Two marketed formulations, standard levodopa/Carbidopa, 100/25 mg (LC-100), and dispersible levodopa/benserazide, 100/25 mg (LB-100), were used as reference formulations for a newly developed dispersible microtablet formulation of levodopa/Carbidopa, 5/1.25 mg (LC-5). The microtablets are intended for individualized dosing of levodopa/Carbidopa in Parkinson disease by means of an electronic dose dispenser with a built-in diary for symptom registration. METHODS: A single-dose, open, randomized, 3-way crossover study was performed in 19 healthy subjects. Concentrations of levodopa, Carbidopa, and the metabolite 3-O-MD in plasma were determined after intake of 100 mg of levodopa, that is, one tablet of reference formulations and 20 microtablets of the new formulation. RESULTS: The LC-5 microtablets were bioequivalent to the LC-100 tablets in area under the curve (AUC) and maximum concentration in plasma (Cmax) for levodopa, and to the LB-100 tablets in AUC. The dispersible levodopa/benserazide formulation showed earlier time to Cmax and significantly higher Cmax for levodopa in plasma compared to the microtablets. Carbidopa showed larger interindividual variation in AUC and Cmax than levodopa, and the bioequivalence comparison LC-5/LC-100 for this compound did not reach the target. Nevertheless, comparison of 3-O-MD levels for LC-5/LC-100, assuming proportionality to levodopa levels, demonstrated bioequivalence. CONCLUSIONS: The new levodopa/Carbidopa microtablets had a pharmacokinetic profile that would allow for a convenient switch of therapy from standard tablets. Frequent dose administration of levodopa/Carbidopa microtablets with an electronic dose dispenser might offer an optimal oral drug delivery in Parkinson disease.