title: Transdermal Delivery of Etoposide Phosphate I: In Vitro and In Vivo Evaluation.
abstract: Cancer chemotherapy frequently requires long periods of multiple intravenous infusions that often results in patients opting out of treatment. The main purpose of this study was to investigate the feasibility of delivering one of these anticancer agents: etoposide phosphate (ETP) transdermally using iontophoresis and a combination of iontophoresis/microporation. The iontophoresis conditions for ETP were first optimized in vitro then tested in vivo in a rabbit model. Both ETP and its active form etoposide (VP) were quantified in dermis (via microdialysis sampling) and in plasma, with a specially developed high-performance liquid chromatography method. In vitro, the amount of total etoposide permeated and the steady state flux increased (p < 0.05) with increase in iontophoretic current densities (100-400 μA/cm(2)). At 300 μA/cm(2), microporation/iontophoresis further improved both parameters by 2- and 2.8-fold, respectively. In vivo, exposure increased proportionally to current density in plasma, whereas dermal concentration dropped significantly at the highest current density. Microporation led to a 50% increase in Cmax and AUClast values in both skin and plasma. In conclusion, a mild current density (300 μA/cm(2)) and a small surface area (10.1 cm(2)) achieved and maintained the minimum effective concentration for the entire duration of electrical current delivery; microporation further increased the plasma concentrations at the same current density.
authors.affiliation: Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, New York 11201.
authors.forename: Hiren
authors.initials: H
authors.lastname: Patel
authors.affiliation: Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, New York 11201.
authors.forename: Abhay
authors.initials: A
authors.lastname: Joshi
authors.affiliation: Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, New York 11201.
authors.forename: Amit
authors.initials: A
authors.lastname: Joshi
authors.affiliation: Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, New York 11201. Electronic address: gstagni@liu.edu.
authors.forename: Grazia
authors.initials: G
authors.lastname: Stagni
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D005047:Etoposide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D007478:Iontophoresis; D007509:Irritants; D017551:Microdialysis; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D011817:Rabbits; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013552:Swine
chemical_list: D000970:Antineoplastic Agents; D007509:Irritants; D009943:Organophosphorus Compounds; C061400:etoposide phosphate; D005047:Etoposide
keywords: anti-cancer; chemotherapy; etoposide; etoposide phosphate; iontophoresis; microdialysis; microporation; rabbit; transdermal