In vivo iontophoresis of fentanyl and sufentanil in rats: pharmacokinetics and acute antinociceptive effects.
Iontophoresis is a process which enhances skin permeation of ionized species by using an electrical field as driving force. The aim of the present study was to investigate whether transdermal iontophoresis of fentanyl or sufentanil could induce therapeutic plasma levels and antinociceptive effect. Fentanyl and sufentanil were introduced in an acidic buffer (acetate buffer 0.01 M at pH 5) at 40 micrograms/mL. A platinum electrode was clamped in an hydrophilic foam soaked with the drug solution and linked to the anode. A cathodic foam reservoir was filled with saline solution. The device was applied on the abdominal skin of hairless rats and direct current (0.17 mA/cm2) was applied for 1 h. Opioid plasma concentrations were monitored. In the experimental conditions used, iontophoresis strongly increased transdermal permeation of the drugs as compared to diffusion. A 1.5 h Tmax was observed. The maximal plasma levels after 1.5 h were 29.3 +/- 14 ng/mL for fentanyl and 29.1 +/- 14 ng/mL for sufentanil. The plasma level of the narcotics decreased slowly after iontophoresis was terminated. Iontophoretic transdermal permeation of fentanyl and sufentanil in rats induced analgesic effects as measured by the tail-flick test. These effects lasted for about 4 h. Thus, transdermal iontophoresis with a miniaturized device is effective for the controlled and pulsatile or sustained delivery of synthetic opiates for pain management in humans. As compared to classical patches, it could reduce the lag time before reaching steady state and allow variable drug release rate.
Thysman
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S
Université Catholique de Louvain, Unité de pharmacie galénique, Ecole de pharmacie, Brussels, Belgium.
Préat
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V
D000279:Administration, Cutaneous; D000818:Animals; D004558:Electric Stimulation; D005283:Fentanyl / Q000097:blood / Q000493:pharmacokinetics*; D007478:Iontophoresis; D008297:Male; D010146:Pain / Q000517:prevention & control*; D051381:Rats; D012869:Skin Absorption; D017409:Sufentanil / Q000097:blood / Q000493:pharmacokinetics*
D017409:Sufentanil; D005283:Fentanyl