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J Appl Physiol (April 30, 2004). doi:10.1152/japplphysiol.00373.2004
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Submitted on April 6, 2004
Accepted on April 26, 2004

The influence of vehicle resistance on transdermal iontophoretic delivery of acetylcholine and sodium nitroprusside in humans

Faisel Khan1*, David J Newton1, Emily C Smyth1, and Jill J Belch1

1 Vascular Diseases Research Unit, The Institute of Cardiovascular Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom

* To whom correspondence should be addressed. E-mail: f.khan{at}dundee.ac.uk.

Iontophoresis is a valuable method of non-invasive drug delivery for assessment of skin microvascular function, but it is important to consider and minimize its potential non-specific electrical effects on blood flow. The use of sodium chloride (NaCl) instead of water as the iontophoresis vehicle has been reported to reduce these effects because it has a lower electrical resistance. However, this argument may not be valid when an agonist is added to the vehicle, as its resistance will be changed. The aim of our study was to determine whether there is a difference in resistance between water and NaCl when used as vehicles for iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Four cumulative doses of each drug, dissolved in either water or NaCl, were delivered via iontophoresis to the forearm skin of 14 healthy volunteers. We measured the resulting blood flow responses using laser Doppler imaging, and the voltage across the electrodes for each delivery as an index of resistance. For ACh and SNP, there were no significant differences between the voltages measured when either water or NaCl was used as the vehicle. However, the blood flow responses to both agonists were significantly lower with NaCl (ACh: 25% lower, P < 0.001; SNP: 15% lower, P = 0.019). The use of NaCl is therefore unlikely to decrease any non-specific electrical effects, and may in fact reduce the effective dose of drug delivered. De-ionized water is a better iontophoresis vehicle for the assessment of microvascular function in skin when using ACh and SNP.




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