Transdermal delivery of fentanyl: rapid onset of analgesia using skin electroporation

被引:45
作者
Vanbever, R
Langers, G
Montmayeur, S
Preat, V [1 ]
机构
[1] Catholic Univ Louvain, Ecole Pharm, Unite Pharm Galen, Brussels, Belgium
[2] Catholic Univ Louvain, Unite Pharm Galen Ind & Officinale, B-1200 Brussels, Belgium
关键词
skin electroporation; fentanyl; transdermal drug delivery; iontophoresis; in vivo;
D O I
10.1016/S0168-3659(97)00147-8
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Skin electroporation has recently been shown to increase transdermal transport of small-size drugs as well as considerably larger molecules by up to 4 orders of magnitude in vitro. Nevertheless, no in vivo studies have proven that high-voltage pulses can induce therapeutic plasma levels of drug. The aim of the present report was precisely to study the potential of skin electroporation in transdermal delivery of fentanyl in vivo, Fentanyl was transdermally delivered to hairless rats using high-voltage pulsing. Following the administration, the pharmacokinetics and pharmacodynamics were assessed. Significant fentanyl plasma concentrations were rapidly achieved using skin electroporation. Immediately after the 5 min pulsing, fentanyl plasma levels reached one third of the maximal plasma concentration of similar to 30 ng/ml, the peak occurring 30 min after the electroporation. Deep analgesia and supraspinal effects were achieved, antinociception lasting for an hour. The magnitude of the effects was, however, dependent on the electrical parameters of the pulses. (C) 1998 Elsevier Science B.V.
引用
收藏
页码:225 / 235
页数:11
相关论文
共 34 条
[1]  
[Anonymous], 1989, DRUGS PHARM SCI
[2]   THE IONTOPHORESIS OF FENTANYL CITRATE IN HUMANS [J].
ASHBURN, MA ;
STREISAND, J ;
ZHANG, J ;
LOVE, G ;
ROWIN, M ;
NIU, S ;
KIEVIT, JK ;
KROEP, JR ;
MERTENS, MJ .
ANESTHESIOLOGY, 1995, 82 (05) :1146-1153
[3]   COMPARATIVE TISSUE CONCENTRATION PROFILES OF FENTANYL AND ALFENTANIL IN HUMANS PREDICTED FROM TISSUE BLOOD PARTITION DATA OBTAINED IN RATS [J].
BJORKMAN, S ;
STANSKI, DR ;
VEROTTA, D ;
HARASHIMA, H .
ANESTHESIOLOGY, 1990, 72 (05) :865-873
[4]   EFFECT OF ELECTROPORATION ON TRANSDERMAL IONTOPHORETIC DELIVERY OF LUTEINIZING-HORMONE-RELEASING HORMONE (LHRH) IN-VITRO [J].
BOMMANNAN, DB ;
TAMADA, J ;
LEUNG, L ;
POTTS, RO .
PHARMACEUTICAL RESEARCH, 1994, 11 (12) :1809-1814
[5]   Continuous intrathecal administration of short-lasting mu opioids remifentanil and alfentanil in the rat [J].
Buerkle, H ;
Yaksh, TL .
ANESTHESIOLOGY, 1996, 84 (04) :926-935
[6]   MECHANISM OF ELECTROINDUCED IONIC SPECIES TRANSPORT THROUGH A MULTILAMELLAR LIPID SYSTEM [J].
CHIZMADZHEV, YA ;
ZARNITSIN, VG ;
WEAVER, JC ;
POTTS, RO .
BIOPHYSICAL JOURNAL, 1995, 68 (03) :749-765
[7]   PLASMA FENTANYL CONCENTRATIONS DURING TRANSDERMAL DELIVERY OF FENTANYL TO SURGICAL PATIENTS [J].
DUTHIE, DJR ;
ROWBOTHAM, DJ ;
WYLD, R ;
HENDERSON, PD ;
NIMMO, WS .
BRITISH JOURNAL OF ANAESTHESIA, 1988, 60 (06) :614-618
[8]   ANALYSIS OF ENHANCED TRANSDERMAL TRANSPORT BY SKIN ELECTROPORATION [J].
EDWARDS, DA ;
PRAUSNITZ, MR ;
LANGER, R ;
WEAVER, JC .
JOURNAL OF CONTROLLED RELEASE, 1995, 34 (03) :211-221
[9]   TISSUE REDISTRIBUTION OF FENTANYL AND TERMINATION OF ITS EFFECTS IN RATS [J].
HUG, CC ;
MURPHY, MR .
ANESTHESIOLOGY, 1981, 55 (04) :369-375
[10]  
LEE LY, 1992, ANN PHARMACOTHER, V26, P1393