Elitech NANODUCT 1030 User Manual page 65

Appendix I: Pilocarpine Iontophoresis: Requirements and Risks
In common with all sweat test procedures for the diagnosis of cystic fibrosis since the inception of the
sweat test, sweat must be induced in order to be analyzed. In modern medical practice the sweat glands
in a limited area of the skin are stimulated by local application of cholinergic drugs, particularly pilocarpine.
These substances are introduced to the glands by iontophoresis (in the case of pilocarpine).
These drugs act by mimicking the action of the natural physiological gland stimulator, acetylcholine, which
is liberated at the gland by signals from the autonomic nervous system. The iontophoretic procedure
depends upon the application of a small and brief direct current to the skin via electrodes, the anode of
which, being positive, drives the positively-charged pilocarpine from the reservoir of drug sufficiently to
reach the glands.
The requirements for Pilocarpine, as defined in the ELITechGroup Quality Procedures, are primarily that
the form and source of the drug be pilocarpine nitrate and the purity being that specified by the United
States Pharmacopeia (USP Grade). The concentration of aqueous pilocarpine nitrate solution should be
sufficient to initiate a maximal sweat-yielding response from the glands. The ELITechGroup concentration
for Nanoduct meets this requirement at a minimal level of 1.5%. Where positively- charged salt ions (acting
as iontophoretic transport competitors) are absent from the drug solution, the requirement may be met by
1.0% pilocarpine. The literature on pilocarpine shows no evidence of allergic sensitivity to the drug.
ELITechGroup gel drug reservoirs are quality controlled to meet these requirements in Pilogels
manufactured in-house, using spectrophotometric procedures to check the pilocarpine content of the gels
in each batch.
Burns Under Iontophoresis
Minor skin burns have been an unwelcome, adverse side-effect of pilocarpine iontophoresis from the
beginning of sweat testing with the Gibson and Cooke method. Unusual sensitivity to pilocarpine has
sometimes been assumed to be the cause of "burns" but there is no firm evidence for this contention.
Majority opinion seems to support the proposition that some types of stimulating apparatus are prone to
cause burns, particularly when associated with procedural error.
ELITechGroup sweat stimulating systems use a sophisticated microprocessor controller with a very low
total delivery current (0.5 milliamperes in the Nanoduct System). Pilocarpine is contained in unique gel
reservoirs. Pilogel Discs for Nanoduct also include compounds that further protect the patient from skin
damage by preventing acid accumulation, by minimizing the risk of gel breakage, and by substantially
reducing the time of electrical drug transport.
These features markedly reduce, but do not entirely eliminate, the possibility of skin burns. Most individuals
that exhibit a sensitivity to pilocarpine experience a mild erythema (redness) at the skin stimulation site.
In some cases, one or more blister-like welts may also form. These are often mistaken for burns, but
are more likely to be a temporary reaction to the passage of electrical current. Such "blisters" invariably
disappear within 2 or 3 hours, leaving no aftereffects.
While the apparent burn rate with the original ELITechGroup Macroduct 3700 system is less than 1 in
50,000 tests, based on current data and reported events, there have been no reported burns using the
original Nanoduct system or the Nanoduct 1030.The low rate is due to ELITechGroup's insistence on
proper test procedures together with built-in equipment safety provisions that minimize the risk of even mild
skin injury. It is highly unlikely that patients will suffer a burn during the stimulation phase of the sweat test.
65