标题：In Vitro and in Vivo Characterization of a Newly Developed Clonidine Transdermal Patch for Treatment of Attention Deficit Hyperactivity Disorder in Children
摘要：The aim of this study was to characterize a newly developed clonidine transdermal patch, KBD-transdermal therapeutic system (TTS), for the treatment of attention deficit hyperactivity disorder in children. In vitro release, penetration, and in vivo pharmacokinetics in rabbits were investigated. The smaller size of KBD-TTS (2.5 mg/2.5 cm2) showed a similar in vitro penetration to those of Catapres-TTS (2.5 mg/3.5 cm2, a clonidine transdermal patch used for the treatment of hypertension, Alza Corporation, U.S.A.). The transdermal penetration rate of clonidine was mainly controlled by the ethylene vinylacetate membrane used in the patch. The skin layer may be only a minor rate-limiting barrier after the topical skin layer at the dosing site is saturated with penetrating clonidine in the initial phase (0 to 12 h). A sensitive liquid chromatography-mass spectrometry method for the quantification of clonidine in rabbit plasma was developed using solid-phase extraction and gradient elution on LC combined with the selected-ion monitoring (SIM) mode. A single dose of clonidine transdermal patch (KBD-TTS) or Catapres-TTS was transdermally administered to rabbits ( n =6 each) and removed after 168 h. The average half-life, T max, C max and C ss values of clonidine in rabbits following administration of KBD-TTS were 19.27±4.68 h, 52.56±25.77 h, 27.39±9.03 ng/ml, and 25.82±9.34 ng/ml, similar to those of Catapres-TTS, respectively. The clonidine plasma concentration of KBD-TTS reached a steady state at 24 h through 168 h. The in vitro release rate of the clonidine from KBD-TTS significantly correlated with the in vivo absorption rate ( p <0.001).
关键词：clonidine;KBD-transdermal therapeutic system (TTS);LC-MS;transdermal penetration;pharmacokinetics;rabbit
