A time-response model for analysis of drug transport and blood flow response during iontophoresis of acetylcholine and sodium nitroprusside.
OBJECTIVE
The analysis of blood flow responses to iontophoresis of vasoactive drugs is often limited to evaluation of maximum responses. In this study, a time-response model is proposed for the blood flow responses to vasoactive drugs applied by iontophoresis.


METHODS
The microvascular bed is represented as a single compartment with a zero-order influx of the drugs from the electrode and a first-order clearance due to diffusion and blood flow. The blood flow response to the local drug dose is described using the E(max) model.


RESULTS
The model accurately describes the blood flow responses to acetylcholine and sodium nitroprusside during a single iontophoretic current pulse. There is a significant clearance out of the microvascular bed during iontophoresis which depends on the type of drug administered.


CONCLUSIONS
The model enables an accurate estimation of response parameters such as ED50 and maximum response, even if the true maximum blood flow is not obtained. The results suggest that due to clearance from the microvascular bed, the local drug dose during a single pulse of current is not linearly proportional to current strength multiplied by pulse duration.
Tesselaar
Erik
E
Department of Medicine and Care, Faculty of Health Sciences, Linköping University Hospital, Linköping, Sweden. e.j.tesselaar@gmail.com
Henricson
Joakim
J
Jonsson
Susanne
S
Sjöberg
Folke
F
D000109:Acetylcholine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000279:Administration, Cutaneous; D000328:Adult; D001783:Blood Flow Velocity; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008955:Models, Cardiovascular; D009599:Nitroprusside / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply*; D012869:Skin Absorption; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055815:Young Adult
D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine