Enhanced transdermal delivery of zidovudine in rats and human skin.
Zidovudine (azidothymidine, AZT), a potent antiviral agent acting on acquired immunodeficiency syndrome virus, was examined with regard to permeation through rat and human skin. A steady state plasma concentration of AZT after transdermal application in rats estimated from both pharmacokinetics data after i.v. administration and penetration rate through excised rat skin from 10% oleic acid (OA) aqueous solution shows penetration about 85 times higher compared to that from 10% OA would be needed for therapeutic efficacy. A mixed-solvent system consisted of 5% Sefsol-318 (S-318), 10% OA, 10% N-methyl-2-pyrrolidone (MP), 20% propylene glycol (PG) and water showed promising characteristics as a vehicle in terms of permeability of AZT through excised rat skin. The maximum flux of 0.41 mumol/cm2/h was observed in excised human skin after application of a gel formulation including S-318, OA, MP and PG. The result suggests a possible use of the gel formulation to gain an effective plasma concentration in humans.
Seki
T
T
Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
Toeda
C
C
Kawaguchi
T
T
Juni
K
K
Sugibayashi
K
K
Morimoto
Y
Y
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption; D015215:Zidovudine / Q000008:administration & dosage / Q000493:pharmacokinetics*
D015215:Zidovudine