A new sublingual formulation of apomorphine in the treatment of patients with Parkinson's disease

Abstract

A new formulation of a sublingual tablet with 10 mg apomorphine was examined in 13 patients with Parkinson's disease. Vitamin C (250 mg) was added sublingually to lower the salivary pH. Four patients received sublingual apomorphine and nine received sublingual apomorphine as well as vitamin C. Subcutaneous apomorphine was given to all patients. The study was designed as a randomized three-way cross-over study. Tmax, Cmax, and bioavailability (F) were determined. Clinical efficacy was assessed by hand-tapping during 30 s, walking time over 25 m, and a 4-point tremor score. The mean Tmax after subcutaneous apomorphine was 14.5 +/- 1.9 min with a mean Cmax of 19.2 +/- 3.8 ng/ml. The mean clearance of all patients was 3.8 +/- 0.6 L/min. The mean Tmax after sublingual apomorphine was 61.1 +/- 6.9 min vs. 61.7 +/- 8.2 min with vitamin C. The mean Cmax was 7.4 +/- 1.0 ng/ml (- vitamin C) vs. 4.3 +/- 1.3 ng/ml (+ vitamin C). These data resulted consequently in a not significantly different mean bioavailability, varying from 17.6% (- vitamin C) to 6.1% (+ vitamin C). The latency of onset of clinical efficacy varied between 25.0 +/- 8.5 min (- vitamin C) and 26.0 +/- 5.3 min (+ vitamin C). The duration of effect was lower (not significantly) when vitamin C was added: 88.0 +/- 12.5 min (- vitamin C) vs. 61.0 +/- 11.9 min (+ vitamin C). These data show that 10 mg apomorphine sublingually was effective in 56% of the patients. The combination with vitamin C did not significantly change the latency of onset or duration of clinical efficacy. Sublingual apomorphine should be considered as an alternative in the treatment of "off"-periods in Parkinson's disease, in particular when patients have the capacity to anticipate their off-periods.

Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled, randomized, double‐blind, cross‐over study

“…This delay was however longer than that induced in the same patients by sc apomorphine (median time to ON 16 minutes on apomorphine versus 30 minutes on S90049). This is in line with previous reports showing that time to ON was also longer when apomorphine was administered sublingually (25–40 minutes) 21–23. However, 50% of the S90049 “responders” switched ON within 30 minutes, a delay that is of clinical interest and might improve if greater doses are to be tested in the future.…”

A Randomized, Double-blind, Placebo-Controlled Trial of Subcutaneously Injected Apomorphine for Parkinsonian Off-State Events

“…5 While an extensive literature exists for apomorphine therapy for PD, only a few studies have been conducted as randomized, placebo-controlled trials using subcutaneous injections of apomorphine to abort offstate events. [6][7][8][9][10][11][12][13][14][15] To our knowledge, only a single study has been previously published evaluating the drug in both inpatient and outpatient settings; in the outpatient setting, all patients received active drug without a placebo comparator. 7 To date there have been no pub-lished studies attempting to correlate inpatient efficacy measures with outpatient results.…”

Intermittent Apomorphine Use for off Period Rescue in Parkinson's Disease: A Pragmatic Review of over Three Decades of Clinical Experience

“…1). Apomorphine administration was: subcutaneous in 29 (50.0%), 5, sublingual in 14 (24.1%), [43][44][45][46][47][48][49][50][51][52][53][54][55][56] intranasal in 6 (10.3%), [57][58][59][60][61][62] inhaled in 5 (8.6%), [63][64][65][66][67] rectal in 3 (5.2%), [68][69][70] and transdermal in 1 (1.7%). 71 54 studies were interventional, most non-randomized open label (33,61.1%), and without control group (25, 46.3%).…”