title: Design of hydrogels of 5-hydroxymethyl tolterodine and their studies on pharmacokinetics, pharmacodynamics and transdermal mechanism.
abstract: development, single-factor experiments were employed to evaluate the effect of adding different matrix, enhancers, 5-HMT, ethanol and glycerol on drug skin development, single-factor experiments were employed to evaluate the effect of adding different matrix, enhancers, 5-HMT, ethanol and glycerol on drug skin permeation. Finally, Carbopol 940 was selected as the gel matrix with N-methyl pyrrolidone (NMP) chosen as the enhancer. The relationship between time and the steady accumulative percutaneous amount (Q, μgcm-2) of optimized 5-HMT hydrogels was Q4-12h=1290.8t1/2-1227.7. The absolute bioavailability of 5-HMT hydrogels was 20.7% showed in pharmacokinetic study. No skin irritation was observed in 5-HMT hydrogels skin irritation study. In the pharmacodynamic study, the overactive bladder model was induced by 150μg/kg of pilocarpine in rats. The significant effects of 5-HMT hydrogels on the inhibition of urine output on rat model were last to 12h. The optimized 5-HMT hydrogels displayed prolonged pharmacological responses. 5-HMT hydrogels effectively avoided the metabolism difference of enzyme in bodies compared with tolterodine tablets, provided one single active compound in plasma to reduce the variability of having two active compounds. To further elucidate the transdermal mechanism, fourier transform infrared (FTIR) spectroscopy, differential scanning calorimeter (DSC) and activation energy measurements were used to study the transdermal routes and changes of stratum corneum during drug release.
authors: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China.
authors: Wenhua
authors: W
authors: Liu
authors: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China.
authors: Lirong
authors: L
authors: Teng
authors: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China.
authors: Kongtong
authors: K
authors: Yu
authors: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China.
authors: Xiangshi
authors: X
authors: Sun
authors: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China.
authors: Chunyu
authors: C
authors: Fan
authors: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China.
authors: Chaoxing
authors: C
authors: Long
authors: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China.
authors: Na
authors: N
authors: Liu
authors: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China.
authors: Shuang
authors: S
authors: Li
authors: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China.
authors: Bing
authors: B
authors: Wu
authors: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China.
authors: Qingji
authors: Q
authors: Xu
authors: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China. Electronic address: sunfengying@jlu.edu.cn.
authors: Fengying
authors: F
authors: Sun
authors: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China. Electronic address: liyouxin@jlu.edu.cn.
authors: Youxin
authors: Y
authors: Li
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D003408:Cresols / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D015195:Drug Design; D005260:Female; D020100:Hydrogels / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D009924:Organ Culture Techniques; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology
chemical_list: C109909:5-hydroxymethyl tolterodine; D001559:Benzhydryl Compounds; D003408:Cresols; D020100:Hydrogels
keywords: 5-Hydroxymethyl tolterodine (5-HMT); Hydrogels; Pharmacodynamics; Pharmacokinetics; Transdermal mechanism