caa a22 4500 477126685 CHVBK 20180405111651.0 cr unu---uuuuu 170330e19971201xx s 000 0 eng 10.1023/A:1012100417645 doi (NATIONALLICENCE)springer-10.1023/A:1012100417645 lontophoretic Delivery of Apomorphine I: In Vitro Optimization and Validation [Elektronische Daten] [Ronald van der Geest, Meindert Danhof, Harry Boddé] Purpose. To investigate the feasibility of transdermal iontophoretic delivery of apomorphine in patients with Parkinson's disease, transdermal transport rates were optimized and validated across human stratum corneum and freshly dermatomed human skin in vitro. Methods. In all experiments R-apomorphine hydrochloride was applied in the anodal compartment. The effect on the flux of the following parameters was studied, using a flow through transport cell: current density, pH, concentration, ionic strength, osmolarity, buffer strength, temperature and skin type. Results. Transdermal transport of apomorphine was directly controlled by the presence or absence of current. Passive delivery was minimal and no depot effect was observed. A linear relationship was found between current density and steady-state flux. At room temperature the lag time was 30 to 40 minutes. A maximal steady-state flux was obtained when the donor concentration approached maximum solubility. By increasing the temperature of the acceptor chamber to 37°C, the steady-state flux was increased by a factor of 2.3 and the lag time decreased to ± 3 minutes. No effect of osmolarity and buffer strength, and only a small effect of ionic strength and pH on the transport rate were observed. The flux through dermatomed human skin was decreased compared to stratum corneum. This effect was shown not to be caused by skin metabolism. Conclusions. The results obtained in vitroindicate that the iontophoretic delivery of apomorphine can be controlled and manipulated accurately by the applied current. The in vitro flux furthermore depends on the donor composition, temperature and skin type. Under optimized conditions, transport rates resulting in therapeutically effective plasma concentrations are feasible, assuming a one to one in vitro/in vivo correlation. Plenum Publishing Corporation, 1997 iontophoresis nationallicence apomorphine nationallicence in vitro/in vivo correlation nationallicence human skin nationallicence skin metabolism nationallicence Parkinson's disease nationallicence van der Geest Ronald 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 Boddé Harry Division of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1798-1803 0724-8741 14:12<1798 1997 14 11095 https://doi.org/10.1023/A:1012100417645 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012100417645 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- Danhof Meindert 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 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1798-1803 0724-8741 14:12<1798 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer