Prolonged Delivery of Apomorphine Through the Buccal Mucosa, Towards a Noninvasive Sustained Administration Method in Parkinson's Disease: In Vivo Investigations in Pigs

Constantin Itin, Rinat Komargodski, Dinorah Barasch, Abraham J. Domb, Amnon Hoffman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

In the current work, prolonged systemic delivery of apomorphine via buccal mucosa was shown to be a promising treatment for Parkinson's disease as a substitute for clinically utilized subcutaneous infusions. Due to extensive ‘first-pass’ metabolism, apomorphine is administered parenterally to bypass liver metabolism. Drawbacks of parenteral administration cause low patient compliance and adherence to treatment. On the other hand, while also bypassing the liver, delivery through buccal mucosa has a superior safety profile, is less costly, lacks pain and discomfort, and possesses excellent accessibility, overall augmenting patient compliance. Current in vivo study in pigs showed: (1) steady plateau levels of apomorphine in plasma were obtained 30 min following administration and remained constant for 8 h until a delivery device was removed, (2) bioavailability of apomorphine was 55%–80% as opposed to <2% peroral and (3) simulation of the pharmacokinetic profile obtained in pigs predicted therapeutically relevant levels of apomorphine in human. Furthermore, antipyrine was incorporated as a permeation marker to enable mechanistic investigation of apomorphine release from the delivery device and its permeation through the buccal mucosa. In addition, limitations of an Ussing diffusion chamber as an ex vivo research tool were also discussed.

Original languageAmerican English
Pages (from-to)1824-1833
Number of pages10
JournalJournal of Pharmaceutical Sciences
Volume110
Issue number4
DOIs
StatePublished - Apr 2021

Bibliographical note

Publisher Copyright:
© 2020

Keywords

  • Antipyrine
  • Apomorphine
  • Bioavailability
  • Buccal
  • Buccal delivery
  • Controlled delivery
  • Drug delivery system
  • Pharmacokinetics
  • Prolonged delivery
  • Transmucosal drug delivery

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