The Quantity and Distribution of Radiolabeled Dexamethasone Delivered to Tissue by Iontophoresis

Abstract

A pilot study was conducted in the first of two monkeys using either radiolabeled Dm-Na-P or radiolabeled hydrocortisone sodium succinate, together with lidocaine HCl. This study indicated an approximately tenfold increase in the quantity of Dm-Na-P delivered to the test electrodes (4 mA; 20 minutes) whereas the quantity of hydrocortisone delivered from the test electrodes was only marginally (approximately 10%) increased as compared with that from the controls. In terms of an anti-inflammatory activity, the effective dose of Dm-Na-P in all tissue layers underlying the test electrodes was at least tenfold that of the hydrocortisone. Therefore, further trials with hydrocortisone were abandoned. In the second animal, positive test electrodes (5 mA; 20 minutes, were sited over five joints on the right side of the body and matching control electrodes (0 mA; 20 minutes) were placed over corresponding joints on the left side of the body. The control and test electrodes each contained 1.0 ml tritium-labeled Dm-Na-P (approximately 4.0 mg) and 2.0 ml 4% lidocaine HCl (80 mg). Local tissue concentrations of Dm-Na-P were higher than those that would be obtained by systematic therapy and lower than would be obtained by local injection.

Failure to Detect Dexamethasone Phosphate in the Local Venous Blood Postcathodic Iontophoresis in Humans

“…Glass and colleagues 6 achieved a calculated 26% delivery efficiency in a previous single-monkey experiment utilizing anodic iontophoresis (5 mA, 20 minutes) with 4 mg/ml dexamethasone phosphate and 40 mg/ml lidocaine, with a current density of 0.94 mA/cm 2 . Drug iontophoretic transport was followed with tritiumlabeled dexamethasone phosphate.…”

“…An initial pharmacokinetic analysis of tritiated dexamethasone phosphate iontophoresis documented that 26% of the drug in the application reservoir at the beginning of iontophoresis was absent at the termination. 6 Glass and colleagues 6 presumed that the absent drug was delivered into the body. The experiment used a single rhesus monkey and split the samples into 5 replicates for statistical purposes.…”

“…However, the iontophoretic parameters used in the investigation do not parallel current clinical use of dexamethasone phosphate iontophoresis. The anode was used for dexamethasone phosphate iontophoresis in the investigation by Glass and colleagues, 6 and the majority of published clinical investigations use the cathode. 2 Additionally, the iontophoretic dosage of 100 mA•min and the current density of 0.94 mA/cm 2 both exceed the parameters used in published clinical investigations or commonly accepted clinical practice.…”

Intravesical Chemotherapy and Chemohyperthermia in Non-Muscle-Invasive Bladder Cancer; An Overview on Drug Administration Technologies and Pharmacokinetics

“…Usually iontophoresis is associated with increased transport of water that will entrain any non-ionized solutes present, a phenomenon termed electro-osmosis. Electroosmosis/electrophoresis is used to describe the current induced convective flow of water in association with ions, which can accelerate the transport of ionized molecules down coulombic gradients, non-ionized polar molecules [40], and ionized molecules against their coulombic gradients [41]. Electroporation implies increasing biological membrane permeability under the influence of an electric field, which increases transport rates down concentration gradients [42].…”

New Frontiers in Intravesical Therapies and Drug Delivery

“…However, it was not until Leduc's experimentation in 1908 that researchers realised the importance of the differences between positive and negative ions and adopted this technique for therapeutic uses. In recent years, iontophoresis has been used for local anaesthesia of the skin [26], to administer corticosteroids to joints and tendons involved in inflammatory processes [27], and for regular transcutaneous administration of drugs [28].…”