Pharmacokinetic Evaluation and Tolerability of Inhaled Dry Powder Levodopa in Parkinson’s Disease Patients
Marianne Luinstra1,2, A Wijnand F Rutgers3, Sebastiaan J Vroegop4, Anja Begeman1, Anne J Lexmond1, Floris Grasmeijer1, Paul Hagedoorn1, Anne H de Boer1 & Henderik W Frijlink1
1 University of Groningen, Pharmaceutical Technology and Biopharmacy, Antonius Deusinglaan 1, 9713 AV Groningen, NL.
2 Martini Hospital, Clinical Pharmacy and Toxicology, Van Swietenplein 1, 9728 NT Groningen, NL.
3 Martini Hospital, Neurology and Clinical Neurophysiology, Van Swietenplein 1, 9728 NT Groningen, NL.
4 Martini Hospital, Pulmonary Diseases, Van Swietenplein 1, 9728 NT Groningen, NL.
Levodopa is effective in relieving motor symptoms that characterize Parkinson’s disease, but several years after diagnosis many patients develop motor fluctuations as a result of a narrowing therapeutic window of levodopa. In combination with a delayed onset of effect of orally administered levodopa due to irregular gastrointestinal absorption this may lead to ‘off periods’, in which the Parkinson’s disease symptoms are poorly controlled. Pulmonary administration of levodopa appears a promising fast-acting alternative to injected apomorphine or orodispersible levodopa tablets to treat these off periods. In this abstract, we present the preliminary pharmacokinetic data of an unblinded single centre, single ascending dose study of inhaled doses of 30 mg and 60 mg levodopa with 2% l-leucine dry powder administered with the Cyclops inhaler in Parkinson’s disease patients. The primary objective of this study was the pharmacokinetic evaluation of inhaled levodopa dry powder. The secondary objective was to assess the tolerability of the airways for inhaled dry powder levodopa. On three consecutive visits, at least seven days apart, the participants received a 30 mg inhalation powder dose (visit 1), 60 mg inhalation powder dose (visit 2) and their regular oral levodopa dose (visit 3). Both 30 mg and 60 mg inhaled levodopa showed a rapid rise in levodopa plasma concentration in the four patients that participated in this study to date. Both doses were well tolerated and no changes in pulmonary function were observed. None of the patients experienced cough during or after inhalation.