UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

The pharmacokinetics and pharmacological effect of (S)-5-OH-DPAT following controlled delivery with transdermal iontophoresis.

Ackaert, OW; De Graan, J; Shi, S; Vreeken, R; Pasqua, OED; Dijkstra, D; Westerink, BH; ... Bouwstra, JA; + view all (2011) The pharmacokinetics and pharmacological effect of (S)-5-OH-DPAT following controlled delivery with transdermal iontophoresis. J Pharm Sci , 100 (7) pp. 2996-3009. 10.1002/jps.22492.

Full text not available from this repository.

Abstract

The pharmacokinetic (PK) and pharmacodynamic (PD) properties of the active (S)-enantiomer of the potent dopamine (DA) agonist 5-hydroxy-2-(N,N,-di-n-propylamino)tetralin (5-OH-DPAT) were investigated in a novel anesthetized animal model. First, the relationship between current density, in vivo transport, and plasma profile was characterized. Second, the effect of the anesthetic mixture, transdermal iontophoresis, and blood sampling on the striatal DA release (PD end point) was investigated. Third, the PK-PD relationship following transdermal iontophoresis was investigated during a controlled reversible pharmacological response. Given that striatal DA levels are unaltered during experimental procedures, this rat model can be used to investigate the PK-PD relationship. The in vivo flux was linearly correlated with the current density, indicating that drug delivery can be titrated by the current density. Following transdermal iontophoresis and intravenous infusion, a strong reversible effect was observed. Compartmental modeling showed that the relationship between plasma concentration and biomarker response is best characterized by an effect compartment, rather than an indirect response model. In addition, covariate analysis suggested that the delivery rate can affect the PD efficiency. Finally, PK-PD analysis revealed that steady delivery rates are translated into continuous dopaminergic stimulation. This can be of benefit for reducing side effects in the symptomatic treatment of Parkinson's disease with 5-OH-DPAT.

Type: Article
Title: The pharmacokinetics and pharmacological effect of (S)-5-OH-DPAT following controlled delivery with transdermal iontophoresis.
Location: United States
DOI: 10.1002/jps.22492
Keywords: 8-Hydroxy-2-(di-n-propylamino)tetralin, Administration, Cutaneous, Anesthetics, Inhalation, Animals, Antiparkinson Agents, Basal Ganglia, Delayed-Action Preparations, Diffusion, Dopamine, Dopamine Agonists, Infusions, Intravenous, Iontophoresis, Isoflurane, Male, Microdialysis, Models, Biological, Nonlinear Dynamics, Rats, Rats, Wistar
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/1401007
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item