Failure to Detect Dexamethasone Phosphate in the Local Venous Blood Postcathodic Iontophoresis in Humans

Abstract

Study Design: A single-blind, 2-factor (4 treatments by 8 time points) repeated-measures study design. Objective: To analytically determine dexamethasone and dexamethasone phosphate concentrations in plasma derived from proximal effluent venous blood, following cathodic iontophoresis. Methods and Measures: Six volunteers received the following dexamethasone phosphate (2.5 ml, 4 mg/ml) treatments to their wrists on separate occasions: cathodic iontophoresis (4 mA, 10 minutes or 4 mA, 20 minutes), passive application (10 or 20 minutes). Plasma samples from the ipsilateral antecubital vein were obtained 10 minutes prior to and half way through the treatment (5 or 10 minutes), at the end of the treatment (10 or 20 minutes), and posttreatment (15, 30, 60, 90, and 120 minutes). The present investigation examined: (1) the sensitivity and linearity of extraction and analysis of dexamethasone and dexamethasone phosphate; (2) the necessity for determining both; and (3) the plasma levels from proximal effluent venous blood following cathodic iontophoresis. Results: The aggregate (n = 18) of the 6-point standard curves were linear for dexamethasone (r Ͼ 0.974) and dexamethasone phosphate (r Ͼ 0.829). In vitro dephosphorylation of dexamethasone phosphate to dexamethasone occurred in plasma at 37°C and during freeze-thaw. Measurable dexamethasone or dexamethasone phosphate concentrations were absent at all time points and under all conditions in the human subjects.Conclusions: These results demonstrate the sensitivity of the current assay and the need for evaluating both forms of the drug, as in vitro dephosphorylation results in the presence of dexamethasone and dexamethasone phosphate in samples. Absence of measurable dexamethasone or dexamethasone phosphate in the proximal effluent venous blood may require re-evaluation of the extent of drug delivery during the clinical iontophoresis of dexamethasone phosphate.

Corticosteroid iontophoresis to treat carpal tunnel syndrome: A double‐blind randomized controlled trial

“…Indeed, other studies demonstrated that iontophoresis formed a depot of the medication at the epidermal and dermal planes. 14,24,25 Using a different paradigm, Smutok et al 26 showed limited depth of penetration of dexamethasone following iontophoresis over the wrist of healthy subjects. Those investigators could not detect a measurable concentration of dexamethasone in the proximal effluent venous blood.…”

The Time Course of Dexamethasone Delivery Using Iontophoresis Through Human Skin, Measured via Microdialysis

“…Variations in our methods from those of previous studies 14,15,30 allowed us to monitor several time points of the transdermal drug delivery of Dex-P during iontophoresis to characterize the rate of accumulation of Dex-total in human tissue. First, the present study used a longer iontophoresis dose than that used in the majority of studies.…”

“…For example, researchers have used indirect methods, such as assessing skin blanching characteristics 2 and venous blood draws, 30 to examine Dex-P delivery. One group of researchers directly measured the concentration of Dex-P in underlying tissues after an iontophoresis treatment using tissue biopsies.…”

Iontophoresis Successfully Delivers Dexamethasone Sodium Phosphate to Dermis as Measured by Microdialysis

“…Mechanistic studies such as this which attempt to support efficacy of the use of iontophoresis to deliver DSP across the skin have used a large variety of technical approaches for estimation of the amount of DSP delivered to the tissues (e.g., observation of cutaneous vasoconstriction, analysis of blood plasma, mass spectrometry assay of extracted connective tissue, and Franz diffusion cells) . The current study is the first to use microdialysis to determine dermal concentration levels of DSP.…”