Pharmacokinetics of acyclovir in rabbit skin after i.v.-bolus, ointment, and iontophoretic administrations.
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).
Stagni
Grazia
G
Division of Pharmaceutics and Industrial Pharmacy, Arnold and Marie Schwartz College of Pharmacy, Long Island University, 75 DeKalb Avenue, Brooklyn, NY 11201, USA. gstagni@liu.edu
Ali
Md Ehsan
ME
Weng
Daniella
D
D000212:Acyclovir / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000279:Administration, Cutaneous; D000818:Animals; D005260:Female; D007262:Infusions, Intravenous; D007478:Iontophoresis / Q000295:instrumentation / Q000379:methods*; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods; D009824:Ointments; D011817:Rabbits; D012867:Skin / Q000187:drug effects* / Q000378:metabolism*
D009824:Ointments; D000212:Acyclovir