Pharmacokinetics of Inhaled Levodopa Administered With Oral Carbidopa in the Fed State in Patients With Parkinson's Disease
| Autor: | Charles Oh, Aaron Ellenbogen, Herbert R. Henney, Ping Zhao, Deena M. Kegler-Ebo, Beth Safirstein |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Levodopa Parkinson's disease Administration Oral 02 engineering and technology 030204 cardiovascular system & hematology Gastroenterology Antiparkinson Agents 03 medical and health sciences Food-Drug Interactions 020210 optoelectronics & photonics 0302 clinical medicine Pharmacokinetics Internal medicine Administration Inhalation 0202 electrical engineering electronic engineering information engineering medicine Humans Pharmacology (medical) Adverse effect Aged Pharmacology Aged 80 and over Cross-Over Studies business.industry Carbidopa Parkinson Disease Middle Aged medicine.disease Crossover study Regimen Tolerability Female business medicine.drug |
| Zdroj: | Clinical therapeutics. 42(6) |
| ISSN: | 1879-114X |
| Popis: | Purpose Levodopa (LD) is the most effective oral pharmacotherapy for the management of motor symptoms in Parkinson's disease. However, LD use is complicated by a progressive shortening of the duration of efficacy of a dose, resulting in episodes of inadequate responsiveness, or OFF periods. OFF periods may also occur unpredictably, partly due to the pharmacokinetic (PK) variability of oral LD, resulting from gastrointestinal dysfunction and from the effects of food on absorption. CVT-301 is a levodopa inhalation powder for the treatment of OFF period symptoms in patients on oral dopa-decarboxylase inhibitor/LD. PK and safety profiles of single dose CVT-301, administered with oral carbidopa (CD) and oral CD/LD, were examined in patients with Parkinson's disease in the fed state. Methods Eligible patients were aged 30–85 years, with a clinical diagnosis of Parkinson's disease and a body mass index of 18–32 kg/m2, and were receiving treatment with a stable regimen that included oral CD/LD (25/100 mg) (total LD, ≤800 mg/d). A high-fat/protein meal was eaten 4–5 h after the administration of the morning oral CD/LD dose. Blood samples for predose PK analysis were obtained after the meal, followed by a single inhaled dose of CVT-301 84 mg (+25 mg of oral CD) or oral CD/LD (25/100 mg) or vice versa in 2 dosing periods in a crossover design. Blood was sampled at 0, 5, 10, 15, 30, and 45 min and at 1, 1.5, 2, 3, and 4 h postdose. Tolerability assessments included treatment-emergent adverse events. Findings Twenty-three patients were enrolled (65.2% male; 87.0% white; mean age, 69.3 years; mean body mass index, 26.9 kg/m2; mean Parkinson's disease duration, 8.2 years; mean baseline LD dosage, 460.9 mg/d; 73.9% at Hoehn and Yahr stage Implications PK properties showed that CVT-301 was more rapidly absorbed, with higher plasma LD concentrations in the first 45 min, and demonstrated lower interpatient variability, than was oral CD/LD in the fed condition. The study findings suggest that CVT-301 can be used without regard to food intake. ClinicalTrials.gov identifier: NCT03887884 . |
| Databáze: | OpenAIRE |
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