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Updated: Jun 20, 2026

Multi-system Monitoring for Identification of Seizures, Arrhythmias and Apnea in Conscious Restrained Rabbits
Published on: March 27, 2021
Pharmacokinetics of amitriptyline in rabbit skin and plasma following iontophoretic administrations
Sejal Patel1, Chinmay Shukla, Gaurav Patel
1Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201, USA.
Background:
Amitriptyline (AMT) is a tricyclic antidepressant with demonstrated local analgesic effects in human skin.
Aim:
We investigated the feasibility and mechanisms of iontophoretic delivery of AMT to rabbit dermis and plasma.
Method:
Two microdialysis probes were inserted into the upper dorsal shaved skin of tranquilized rabbits. After 1 hour, an iontophoresis cartridge was placed on top of one probe. The cartridge consisted of a stainless steel electrode covered with a pad that was filled with a 4.3 % AMT glycerin/water (50:50). Iontophoresis was performed at 100, 200, or 300 microA/cm(2) constant-current density for 60 minutes. Dialysate samples were collected every 8 minutes for 3 hours and analyzed for AMT via a validated high-performance liquid chromatographic assay. Retrodialysis was performed at the other site. Blood samples were collected serially for 4 hours.
Results:
In vivo retrodialysis recovery was 89 +/- 2%. AMT skin exposure increased non-proportionally with current density: AUCs were 19 +/- 7, 119 +/- 56, and 615 +/- 302 mg/L/min for the 100, 200, and 300 muA/cm(2), respectively, and C(max) were 107 +/- 15, 1070 +/- 537, and 5870 +/- 1289 microg/L. In vivo plasma concentrations were always below LLOQ (0.1 microg/mL).
Conclusion:
AMT can be administered by iontophoresis and produces significant skin concentrations and negligible plasma levels.
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