Clinical Pharmacokinetics of Buffered Propranolol Sublingual Tablet (Promptol (TM))-Application of a New "Physiologically Based" Model to Assess Absorption and Disposition
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香港中文大學研究人員

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摘要Sublingual administration of certain buffered propranolol may improve the rate and extent of absorption compared to oral administration. The main objectives of this study were to (1) compare the plasma propranolol concentrations (Cp-prop) following sublingual administration of a specially buffered formulation (Promptol (TM)) to that following oral administration of Inderal (R) and (2) evaluate the utility of a special pharmacokinetic model in describing the Cp-prop following sublingual administration. Eighteen healthy volunteers received 10 mg sublingual Promptol (TM) or oral Inderal (R). Multiple Cp-prop were determined and their pharmacokinetics compared. Additional data following sublingual 40 mg Promptol (TM) or Inderal (R) were utilized for evaluation of a special advanced compartmental absorption and transit (ACAT) model. For model simulation, the physicochemical parameters were imported from AMET predictor, whereas the pharmacokinetic parameters were calculated and optimized by Gastroplus (R). Based on this model, the quantity of drug absorbed via buccal/sublingual mucosa was estimated. Cp-prop was higher at earlier times with 3-fold greater relative bioavailability following sublingual Promptol (TM) compared to that from oral Inderal (R). The special ACAT model provided excellent goodness of fit of Cp-prop-time curve and estimated a 56.6% increase in absorption rate from Promptol (TM) and higher initial Cp-prop compared to the regular formulation. The modified ACAT model provided a useful approach to describe sublingual absorption of propranolol and clearly demonstrated an improvement of absorption of Promptol (TM). The sublingual 10 mg Promptol (TM) achieved not only a similar systemic exposure as 30 mg oral Inderal (R) but an earlier effective Cp-prop which may be advantageous for certain clinical conditions.
著者Wang YF, Wang ZJ, Zuo Z, Tomlinson B, Lee BTK, Bolger MB, Chow MSS
期刊名稱AAPS Journal
出版年份2013
月份7
日期1
卷號15
期次3
出版社SPRINGER
頁次787 - 796
國際標準期刊號1550-7416
語言英式英語
關鍵詞ACAT; buffered; pharmacokinetics; propranolol; sublingual
Web of Science 學科類別Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY

上次更新時間 2021-02-03 於 01:20