Therapeutic advances in chronic disease · 2019
Pharmacokinetics and tolerability of inhaled levodopa from a new dry-powder inhaler in patients with Parkinson's disease.
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Luinstra Marianne, Rutgers Wijnand, van Laar Teus, Grasmeijer Floris, Begeman Anja, Isufi Valmira, Steenhuis Luc, Hagedoorn Paul, de Boer Anne, Frijlink Henderik W
Аннотация
BACKGROUND: Inhaled levodopa may quickly resolve off periods in Parkinson's disease. Our aim was to determine the pharmacokinetics and tolerability of a new levodopa dry-powder inhaler.
METHODS: A single-centre, single-ascending, single-dose-response study was performed. Over three visits, eight Parkinson's disease patients (not in the 'off state') received by inhalation 30 mg or 60 mg levodopa, or their regular oral levodopa. Maximum levodopa plasma concentration (C max), time to maximum plasma concentration (Tmax) and area under the concentration time curve 0-180 min were determined. Spirometry was performed three times at each visit.
RESULTS: After inhalation, levodopa T max occurred within 15 min in all participants, whereas after oral administration, T max ranged from 20 min to 90 min. The bioavailability of inhaled levodopa without carboxylase inhibitor was 53% relative to oral levodopa with carboxylase inhibitor. No change in lung-function parameters was observed and none of the patients experienced cough or dyspnoea. No correlation was observed between inhalation parameters and levodopa pharmacokinetic parameters.
CONCLUSION: Inhaled levodopa is well tolerated, absorbed faster than oral levodopa, and can be robustly administered over a range of inhalation flow profiles. It therefore appears suitable for the treatment of off periods in Parkinson's disease.
METHODS: A single-centre, single-ascending, single-dose-response study was performed. Over three visits, eight Parkinson's disease patients (not in the 'off state') received by inhalation 30 mg or 60 mg levodopa, or their regular oral levodopa. Maximum levodopa plasma concentration (C max), time to maximum plasma concentration (Tmax) and area under the concentration time curve 0-180 min were determined. Spirometry was performed three times at each visit.
RESULTS: After inhalation, levodopa T max occurred within 15 min in all participants, whereas after oral administration, T max ranged from 20 min to 90 min. The bioavailability of inhaled levodopa without carboxylase inhibitor was 53% relative to oral levodopa with carboxylase inhibitor. No change in lung-function parameters was observed and none of the patients experienced cough or dyspnoea. No correlation was observed between inhalation parameters and levodopa pharmacokinetic parameters.
CONCLUSION: Inhaled levodopa is well tolerated, absorbed faster than oral levodopa, and can be robustly administered over a range of inhalation flow profiles. It therefore appears suitable for the treatment of off periods in Parkinson's disease.