A Time-Response Model for Analysis of Drug Transport and Blood Flow Response during Iontophoresis of Acetylcholine and Sodium Nitroprusside

Abstract

Background/Aims: 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. Conclusion: 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.

Prostaglandins and Radical Oxygen Species Are Involved in Microvascular Effects of Hyperoxia

“…The application of the E max model to perfusion response data obtained from a single-pulse iontophoresis protocol has been validated in previous studies by our group [22,23]. This approach offers important advantages over more qualitative descriptions of responses.…”

Transdermal iontophoresis as an in-vivo technique for studying microvascular physiology

“…Also, it is likely that the true physiological maximum response to the drug is never reached during the experiments because the maximum concentration of the drug in the skin is limited by the local removal of the drug. This is more likely to be a problem with vasodilator drugs than vasoconstrictors, since the removal by local blood flow is increased due to the action of the vasodilator itself (Tesselaar et al, 2009). (Tesselaar et al, 2009).…”

“…This is more likely to be a problem with vasodilator drugs than vasoconstrictors, since the removal by local blood flow is increased due to the action of the vasodilator itself (Tesselaar et al, 2009). (Tesselaar et al, 2009).…”

Implications for burn shock resuscitation of a new in vivo human vascular microdosing technique (microdialysis) for dermal administration of noradrenaline

“…Similar pharmacodynamic effects based on blood flow were shown in another "in vivo" human skin model when the drug was given by iontophoresis. Quantification of local pharmacodynamic variables such as ED 50 and Hill slope for the effect of blood flow is feasible [19]. If this is possible for both the effects of blood flow and for metabolic measurements as shown in the present model, complementary experiments seem warranted in the future.…”