title: Failure to detect dexamethasone phosphate in the local venous blood postcathodic lontophoresis in humans.
abstract: METHODS
  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
  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 > 0.974) and dexamethasone phosphate (r > 0.829). In vitro dephosphorylation of dexamethasone phosphate to dexamethasone occurred in plasma at 37 degrees 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.
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood*; D005260:Female; D006801:Humans; D007478:Iontophoresis; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014953:Wrist
chemical_list: C004180:dexamethasone 21-phosphate; D003907:Dexamethasone