Single- and Multiple-dose Pharmacokinetics of a Novel Tetramethylpyrazine Reservoir-type Transdermal Patch Versus Tetramethylpyrazine Phosphate Oral Tablets in Healthy Normal Volunteers, and In Vitro/In Vivo Correlation

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概要

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• A novel reservoir-type transdermal system of TMP was developed containing eucalyptus oil as a penetration enhancer. The single and multiple-dose pharmacokinetic profiles of TMP administrated by TMP transdermal patch were characterized in healthy volunteers using an in vivo, randomized, open-label, two-way crossover design. TMPP oral tablets were chosen as reference. Following single/multiple oral administration of 200/100 mg TMPP tablets, a TMP Cmax of 1284/613.5 ng/ml was observed within 0.75 h. Single/multiple applications of the TMP patch yielded mean Cmax of 309/325 ng/ml at a median Tmax of 5/4 h, with steady state achieved at second application. The mean Cmin of the patch was 131 ± 30.38 ng/ml, contrasting to nearly zero for the tablet. Multiple applications of patch produced an accumulative effect over single application. At steady state 250 mg/20 cm2 TMP patch given daily provided comparable exposure to 100 mg TMPP tablets three times daily (3753.91 versus 3563.67 ng·h/ml). TMP tablets and patch yielded similar steady-state plasma concentrations: Cav (148.48 ± 51.27 and 156.41 ± 40.31 ng/ml). The results demonstrated that TMP patch can achieve a therapeutic effect that is comparable to oral administration, exhibited prolonged and sustained plasma levels, fewer drug fluctuations, lower adverse effects, more convenience, and improved patient compliance. In-vitro permeation through human skin demonstrated zero-order kinetics with the flux of 364 μg/cm2/h. The predicted Cav (163.9 ng/ml) was in agreement with the observed Cav (156.4 ng/ml).

著者

• Zhang Jianfang

  Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University

• Xu Huinan

  Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University

• Shen Teng

  Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University

• Weng Weiyu

  School of Pharmacy, East China University of Science and Technology

関連論文

• Single- and Multiple-dose Pharmacokinetics of a Novel Tetramethylpyrazine Reservoir-type Transdermal Patch Versus Tetramethylpyrazine Phosphate Oral Tablets in Healthy Normal Volunteers, and In Vitro/In Vivo Correlation

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