Oral sildenafil increases skin hyperaemia induced by iontophoresis of sodium nitroprusside in healthy volunteers.
OBJECTIVE
Sildenafil, a specific inhibitor of phosphodiesterase 5A (PDE5A), is currently tested as a treatment for severe Raynaud's phenomenon. Here, we tested whether sildenafil, alone or combined with local sodium nitroprusside (SNP) delivered through skin iontophoresis, increased forearm cutaneous blood conductance in healthy volunteers, and to assess how well this combination was tolerated.


METHODS
Ten healthy volunteers were enrolled. Variations in cutaneous vascular conductance (CVC) following oral administration of 50 or 100 mg of sildenafil with or without SNP iontophoresis were expressed as a percentage of maximal CVC, and were monitored using laser Doppler imaging. SNP iontophoresis was performed on the ventral surface of the forearm, 1 h after application of lidocaine/prilocaine cream.


RESULTS
Sildenafil at 100 mg, but not 50 mg, increased overall responses (area under the curve) (44%) and peak responses (29%) to SNP iontophoresis. Sildenafil at 100 mg, but not 50 mg, increased baseline CVC (75%). Incidence of headache was not changed when SNP iontophoresis was combined with sildenafil. One episode of symptomatic arterial hypotension occurred in a volunteer given 50 mg sildenafil, 30 min after the beginning of SNP iontophoresis.


CONCLUSIONS
Oral sildenafil at 100 mg potentiated local skin hyperaemia induced by SNP iontophoresis, with no increased incidence of headaches. The combination of oral specific PDE5A inhibitor and nitrates administered through skin iontophoresis deserves further investigation in diseases such as severe Raynaud's phenomenon, with particular attention to the incidence of arterial hypotension.
Blaise
S
S
Inserm CIC3, Grenoble Clinical Research Center, Grenoble University Hospital, Grenoble, France. sblaise@chu-grenoble.fr
Hellmann
M
M
Roustit
M
M
Isnard
S
S
Cracowski
J L
JL
D000284:Administration, Oral; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006940:Hyperemia / Q000139:chemically induced*; D007478:Iontophoresis; D008297:Male; D009599:Nitroprusside / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D000068677:Sildenafil Citrate; D012867:Skin / Q000098:blood supply / Q000187:drug effects*; D013450:Sulfones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009599:Nitroprusside; D000068677:Sildenafil Citrate