Abstract Details

Title Variability of Plasma Levodopa Conveniently Reduced by More Frequent Administration of Smaller Doses of Carbidopa/Levodopa Using a Novel Functionally Scored Formulation

Topic Movement Disorders

Presentation(s) P7 - Poster Session 7 (8:00 AM-9:00 AM)

Poster/Presentation
Number 5-002

Objective

To evaluate the pharmacokinetics (PK) of 25/100 mg carbidopa (CD)/levodopa (LD) compared to half that amount given twice as often using a new, deeply scored, bi-layered tablet.

Background

LD combined with CD has long been the mainstay of Parkinson’s disease (PD) treatment. But with disease progression, patients typically must adjust dose and dose frequency to best manage OFF time and dyskinesias. Current CD/LD formulations fail to provide dosing flexibility. A novel functionally scored tablet was developed to enable precise dosing and improve patient convenience by facilitating easy dose fractionation into four equal 6.25/25 mg CD/LD segments.

Design/Methods Twenty-two healthy adults, aged 35–71 years, were given a whole functionally scored CD/LD 25/100 mg tablet every 4 hours two times. Following a washout period of at least 40 hours, participants received a half-tablet containing CD/LD 12.5/50 mg every 2 hours four times. PK was evaluated every 30 minutes for 12 hours on both study days, along with careful safety monitoring.

Results

Total LD exposure (area under the curve) and time to peak plasma concentration (T_max) did not differ significantly between subjects given the full dose every 4 hours and those given the half-dose every 2 hours. However, with the more frequent administration of a lower dose, peak LD exposure (C_max) declined by 44% (p<0.0001), and the difference between C_max and C_min diminished significantly (p<0.0001). Variance in plasma LD concentrations declined by 51% in the lower, more frequent dose group. Adverse events, none clinically significant, occurred less frequently (41% vs. 9%) in the lower, more frequent dose group.

Conclusions

More frequent administration of lower doses of CD/LD enabled by a newly designed, deeply scored tablet may improve the stability of circulating LD levels and thus potentially improve tolerability and reduce the risk of motor complications in patients with PD.

Authors/Disclosures
Ahmad M. Al-Sabbagh, MD (Avion Pharmaceuticals) PRESENTER	Dr. Al-Sabbagh has nothing to disclose.
	No disclosure on file
Darshana Shah, PhD (Avion Pharmaceuticals)	Dr. Shah has received personal compensation for serving as an employee of Avion Pharmaceuticals.
	No disclosure on file
Kathleen E. Clarence-Smith, MD, PhD, FAAN (KM Pharmaceuticals Consulting)	Dr. Clarence-Smith has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Riverside Pharmaceutical Corporation. Dr. Clarence-Smith has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for KMPHC. Dr. Clarence-Smith has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Chase Therapeutics Corporation. Dr. Clarence-Smith has received stock or an ownership interest from Chase Therapeutics Corporation. Dr. Clarence-Smith has received stock or an ownership interest from Riverside Pharmaceuticals Corporation.
Thomas N. Chase, MD (GT Pharmaceuticals, Inc)	Dr. Chase has received personal compensation for serving as an employee of Chase Therapeutics Corporation. Dr. Chase has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Riverside Pharmaceuticals Corporation. Dr. Chase has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Chase Therapeutics Corporation. Dr. Chase has received stock or an ownership interest from Chase Therapeutics Corporation. Dr. Chase has received stock or an ownership interest from Riverside Pharmaceuticals Corporation.

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