caa a22 4500 477126677 CHVBK 20180405111651.0 cr unu---uuuuu 170330e19971201xx s 000 0 eng 10.1023/A:1012152401715 doi (NATIONALLICENCE)springer-10.1023/A:1012152401715 lontophoretic Delivery of Apomorphine II: An In Vivo Study in Patients with Parkinson's Disease [Elektronische Daten] [Ronald van der Geest, Teus van Laar, Josy Gubbens-Stibbe, Harry Boddé, Meindert Danhof] Purpose. Transdermal transport rates of the dopamine agonist R-apomorphine were determined in patients with idiopathic Parkinson's disease (IPD). Apomorphine was applied by iontophoresis at two current densities. Methods. In ten patients apomorphine was applied passively for one hour. Thereafter, in the first five patients, a current density of 250 μA.cm−2 was applied for one hour and a current density of 375 μA.cm−2 in the second group. The individual pharmacokinetic parameters were obtained separately following a 15-minute zero-order intravenous infusion of 30 μg.kg−1. Skin resistance was measured during current 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, rigidity or cramp) were also recorded. Results. In all patients increasing plasma concentrations of R-apomorphine were found during the interval of current application. The maximum concentrations that were attained were related to the applied current density: 1.3 ± 0.6 ng.ml−1 at 250 μA.cm−2 and 2.5 ± 0.7 ng.ml−1 at 375 μA.cm−2. When the current was switched off all concentrations returned to baseline values in about 90 minutes. By mathematical deconvolution of the profiles it was shown that steady-state fluxes were reached within the one-hour interval of current driven transport. Steady-state fluxes were calculated to be 69 ± 30 nmol.cm−2.h−1 at 250 μA.cm−2 and 114 ± 34 nmol.cm−2.h−1 at 375 μA.cm−2. Individual drug input rates were inversely related to the overall resistance. Significantly elevated LDF values were found after patch removal, indicating mild current induced erythema. Only subtherapeutic plasma concentrations were obtained in all patients except for one. Conclusions. The results show that current-dependent delivery of apomorphine is possible in vivo at acceptable levels of skin irritation. Excellent correlation was found between the calculatedin vivo transport rates and the rates that were previously obtained in vitro. Plenum Publishing Corporation, 1997 iontophoresis nationallicence Parkinson's disease nationallicence human nationallicence pharmacodynamics nationallicence transdermal delivery nationallicence apomorphine nationallicence van der Geest Ronald Division of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands aut van Laar Teus Department of Neurology, Leiden University Hospital, Leiden University, Leiden, The Netherlands aut Gubbens-Stibbe Josy Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands aut Boddé Harry Division of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands aut Danhof Meindert Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1804-1810 0724-8741 14:12<1804 1997 14 11095 https://doi.org/10.1023/A:1012152401715 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012152401715 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- van der Geest Ronald Division of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands aut NATIONALLICENCE 700 1- van Laar Teus Department of Neurology, Leiden University Hospital, Leiden University, Leiden, The Netherlands aut NATIONALLICENCE 700 1- Gubbens-Stibbe Josy Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands aut NATIONALLICENCE 700 1- Boddé Harry Division of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands aut NATIONALLICENCE 700 1- Danhof Meindert Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1804-1810 0724-8741 14:12<1804 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer