IONTOPHORETIC DELIVERY OF APOMORPHINE II - AN IN-VIVO STUDY IN PATIENTS WITH PARKINSONS-DISEASE

Purpose. Transdermal transport rates of the dopamine agonist R-apomorp hine were determined in patients with idiopathic Parkinson's disease ( IPD). Apomorphine was applied by iontophoresis at Two current densitie s. Methods. In ten patients apomorphine was applied passively for one hour. Thereafter, in the first five patients, a current density of 250 mu A.cm(-2) was applied for one hour and a current density of 375 mu A.cm(-2) in the second group. The individual pharmacokinetic parameter s were obtained separately following a 15-minute zero-order intravenou s infusion of 30 mu g.kg(-1). Skin resistance was measured during curr ent delivery. Current-induced irritation was measured by Laser Doppler Flowmetry (LDF). The pharmacodynamics were quantified by a unilateral tapping score. Qualitative clinical improvements (decreased tremor, r igidity or cramp) were also recorded. Results. In all patients increas ing plasma concentrations of R-apomorphine were found during the inter val of current application. The maximum concentrations that were attai ned were related to the applied current density: 1.3 +/- 0.6 ng.ml(-1) at 250 mu A.cm(-2) and 25 +/- 0.7 ng.ml(-1) at 375 mu A.cm(-2). When the current was switched off all concentrations returned to baseline v alues in about 90 minutes. By mathematical deconvolution of the profil es it was shown that steady-state fluxes were reached within the one-h our interval of current driven transport. Steady-state fluxes were cal culated to be 69 +/- 30 nmol.cm(-2).h(-1) at 250 mu A.cm(-2) and 114 /- 34 nmol.cm(-2).h(-1) at 375 mu A.cm(-2), Individual drug input rate s were inversely related to the overall resistance. Significantly elev ated LDF values were found after patch removal, indicating mild curren t induced erythema. Only subtherapeutic plasma concentrations were obt ained in all patients except for one. Conclusions. The results show th at current-dependent delivery of apomorphine is possible in vivo at ac ceptable levels of skin irritation. Excellent correlation was found be tween the calculated in vivo transport rates and the rates that were p reviously obtained in vitro.