Inhalable levodopa: from laboratory to the patient

Levodopa is effective in alleviating the motor symptoms of Parkinson’s disease, but a high variability in levodopa absorption from the gastrointestinal tract after oral administration causes fluctuations in the levodopa plasma concentration. Pulmonary administration of levodopa may offer an attractive alternative to oral administration, die to the larger size of the absorption membrane and the relatively low metabolic activity in the lungs. For that reason, Marianne Luinstra assessed the ability of Parkinson’s disease patients to use a dry powder inhaler (Cyclops) suitable for the administration of a high dose of levodopa during an off period. Further, she developed a levodopa inhalation powder with a very low amount of excipient, using the simple particle preparation technique micronization. Next, she performed a pilot study where she assessed the pharmacokinetics and tolerability of the levodopa with 2% l-leucine inhalation powder from the Cyclops inhaler. Luinstra performed a single center, single ascending dose response study in eight Parkinson’s disease patients. It was observed that, after inhalation, the maximum levodopa blood level occurred between 5 to 15 minutes. After oral administration, the time to maximum levodopa blood level varied considerably more and ranged from 20 to 90 minutes. None of the patients experienced cough or dyspnea and no change in pulmonary function was measured. Additionally, Luinstra assessed the user ability and convenience of the Cyclops inhaler in 60 Parkinson’s patients. Both correct opening of the pouch the inhaler is stored in and correct opening of the inhaler were assessed.

Promotores: Prof.dr. H.W. Frijlink and Prof.dr. T. van Laar