Transdermal iontophoretic delivery of apomorphine in patients improved by surfactant formulation pretreatment.
The objective of the present study is to evaluate the efficacy and the safety of transdermal iontophoretic delivery of R-apomorphine, a potent dopamine agonist, in combination with surfactant pretreatment in patients with advanced Parkinson's disease. Iontophoresis patches were applied in 16 patients for 3.5 h, with 0.5 h of passive delivery followed by 3 h of current application at a current density of 250 microA/cm2. Eight of these patients were treated with a surfactant formulation prior to iontophoresis. The pharmacokinetics, pharmacodynamic effects, systemic and local side effects of R-apomorphine were assessed. The plasma concentration vs. time profiles upon iontophoresis of R-apomorphine were described successfully by a novel pharmacokinetic model. The model suggests that only 1.9% of the dose that has been released from the patch accumulated in the skin. The patients treated with the surfactant formulations showed a statistically significant increase of bioavailability (from 10.6+/-0.8% to 13.2+/-1.4%) and of the steady state input rate (from 75.3+/-6.6 to 98.3+/-12.1 nmol/cm2 h) compared to the control patients (iontophoresis without absorption enhancers). In five out of eight patients in the study group and in three out of eight patients in the control group, clinical improvement was observed.
Li
G L
GL
Department of Pharmaceutical Technology, Leiden Amsterdam Centre for Drug Research, University of Leiden, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.
de Vries
J J
JJ
van Steeg
T J
TJ
van den Bussche
H
H
Maas
H J
HJ
Reeuwijk
H J E M
HJ
Danhof
M
M
Bouwstra
J A
JA
van Laar
T
T
D000279:Administration, Cutaneous; D000368:Aged; D001058:Apomorphine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007478:Iontophoresis; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D013501:Surface-Active Agents / Q000008:administration & dosage*
D013501:Surface-Active Agents; D001058:Apomorphine