Advances in the delivery of treatments for Parkinson's disease.
Innovative drug delivery in Parkinson's disease (PD) has the potential to reduce or avoid many side effects of current treatment, such as wearing-off type fluctuations, dyskinesia, on-off phenomena or bouts of motor freezing. The traditional orally administered formulations of l-dihydroxyphenylalanine combined with a peripheral aromatic acid decarboxylase inhibitor remain the mainstay of treatments for PD. However, such combination therapies have been further formulated to extend their duration of action by including a catechol-O-methyltransferase inhibitor. Preventing the breakdown of dopamine has also been achieved by monoamine oxidase-B inhibition; this approach now having been formulated for sublingual use (Zelapar, Valeant Pharmaceuticals). An alternative approach bypasses the oral route of administration and instead relies on continuous duodenal infusion (Duodopa, Solvay, NeoPharma AB) for better therapeutic effect. The clinical use of dopamine agonists as antiparkinsonian drugs now incorporates a variety of delivery techniques. For example, apomorphine, which relies on parenteral administration for maximum bioavailability, may be delivered via rectal, intranasal, sublingual and subcutaneous (e.g., Apokyn, Mylan Bertek) routes. Meanwhile, rotigotine and lisuride have both been formulated for delivery via skin patches. Finally, the authors examine more experimental delivery techniques, including the delivery of genes via viral vectors or liposomes, intracranial transplant of a variety of cells and of L-dihydroxyphenylalanine by prodrug-dispensing liposomes or pulmonary delivery (AIR, Alkermes). The advent and application of these varied technologies will help encourage patient-specific means of treatment for PD.
Johnston
Tom H
TH
Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, ON M5T 2S8, Canada.
Fox
Susan H
SH
Brotchie
Jonathan M
JM
D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D065098:Catechol O-Methyltransferase Inhibitors; D002626:Chemistry, Pharmaceutical; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000639:trends; D004409:Dyskinesia, Drug-Induced / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D005544:Forecasting; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy*
D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D003692:Delayed-Action Preparations; D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D007980:Levodopa