Pharmacokinetics of acyclovir in rabbit skin after i.v.-bolus, ointment, and iontophoretic administrations

Int J Pharm. 2004 Apr 15;274(1-2):201-11. doi: 10.1016/j.ijpharm.2004.01.024.


The aim of this study was to characterize and compare the pharmacokinetics of acyclovir (ACV) in skin and plasma after iontophoresis, i.v.-bolus, and ointment administrations in rabbit. On five occasions, each separated by at least 1-week washout, rabbits received a 10 mg/kg dose of ACV as i.v.-bolus, ACV iontophoresis for 1 h at different current densities (100, 200, 300 microA/cm2) or a commercially available ointment for two hours. Blood samples were collected serially up to 6 h. Skin ACV concentrations were monitored via microdialysis using linear microdialysis probes (1 cm window). Cathodic iontophoresis was performed using commercially available patches (10 cm2 contact area). Following i.v.-bolus, C(max) in skin occurred with a delay of 38 +/- 4 min compared with plasma. No quantifiable concentration of ACV was detected in the skin on passive drug delivery. Following iontophoresis, skin exposure to ACV was 40, 22, and 11% of that following i.v.-bolus. Conversely, systemic exposure to ACV was negligible and plasma concentrations were below the limit of quantification at any time-point. In skin dialysate, C(max), AUC, and half-life increased with current density. During ointment application, ACV in dermis was detectable only for the first 30 min thereafter ACV skin concentrations were below the LOQ (30 ng/ml).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / administration & dosage*
  • Acyclovir / pharmacokinetics*
  • Administration, Cutaneous
  • Animals
  • Female
  • Infusions, Intravenous
  • Iontophoresis / instrumentation
  • Iontophoresis / methods*
  • Microdialysis / instrumentation
  • Microdialysis / methods
  • Ointments
  • Rabbits
  • Skin / drug effects*
  • Skin / metabolism*


  • Ointments
  • Acyclovir