ANA: Preloaded Apomorphine Pen Offers Delivery Similar to Manually Filled Syringe

[Murray Charters <mcharters@xxxxxxxxxxxxxx>]

ANA: Preloaded Apomorphine Pen Offers Delivery Similar to Manually Filled 
Syringe
By Paula Moyer

SAN FRANCISCO, CA -- November 6, 2003 -- A preloaded "pen" containing 
apomorphine HCL delivers the drug precisely and
accurately, with bioavailability similar to that used in syringes that are 
manually filled with either cartridges or
ampoules. These findings were presented here October 21st at the 128th Annual 
Meeting of the American Neurological
Association.

This news should be encouraging for neurologists, who are seeking ways to help 
patients with Parkinson's disease treat
"off episodes," according to investigator Terri L. Murton, PhD. Apomorphine is 
a short-acting dopamine agonist that has
been investigated for the treatment of such episodes.

"We found no difference among the pen, the cartridge and the ampoule delivery 
systems," said Dr. Murton, senior
research scientist, Pharmacokinetics and Drug Metabolism Division, Mylan 
Pharmaceuticals, Morgantown, West Virginia,
United States. "The cartridge and ampoule are easy to administer without 
excessive adverse effects, although the pen
has convenience advantages." Dr. Murton noted that clinical trials on 
apomorphine have been concluded, and that Mylan,
the manufacturer, received approval from the United States Food and Drug 
Administration for apomorphine in January
2003.

In an open-label, 3-way crossover study, Dr. Murton and co-investigators 
investigated the absorption of an apomorphine
injection consisting of 10 mg/ml after administration with the pen device. The 
researchers compared the absorption
after administration with the pen to that following administration from the 
ampoule or the cartridge. The single-use
ampoules were pre-filled; the cartridges used a formulation designed for 
multiple uses containing 0.05% benzyl alcohol,
which is instilled into a cartridge and injected with a syringe.

The investigators recruited 35 healthy volunteers for the study. The subjects 
were between 18 and 55 years old and
within 15% of their ideal body weight. To ward off treatment-related nausea and 
vomiting, the subjects received
concurrent prophylactic treatment consisting of the anti-emetic 
trimethobenzamide.

The subjects all received 2-mg/0.02 mL subcutaneously with the pen device, with 
the syringe and ampoule, and with the
cartridge. The investigators then assessed the subjects' plasma drug levels by 
liquid chromatography and mass
spectrometry, and they estimated the pharmacokinetics parameters from the 
resulting concentration time curves for each
delivery device and formulation.

Dr. Murton and her investigative team found that the 90% confidence intervals 
showed bioequivalence (80%-125%) of
natural-log transformed parameters among the 3 systems in area-under-curve 
(AUC) and peak concentration (CPeak)
analyses (AUC[0-t], AUC[0-inf], Cpeak). This bioequivalence signified that the 
pen device did not affect the drug's
relative bioavailability, the investigators stated.

Among the 35 subjects, 34 completed the study. The investigators documented 31 
adverse events among 12 subjects. The
most common adverse events were headache, vomiting, and nausea.

This study was sponsored by Mylan Pharmaceuticals and its subsidiary, Bertek 
Pharmaceuticals.

[Study Title: A Phase I, Open-Label, Three-Way Crossover Study in Healthy 
Volunteers to Compare the Pharmacokinetics of
Apomorphine HCL Delivered From a Cartridge Using a Pen Device to That Delivered 
Using a Syringe Manually Filled from
Either a Cartridge or an Ampoule. Abstract 213]

SOURCE: Doctor's Guide (press release)


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