Wood R W, Martis L, Gillum A W, Roseman T J, Lin L, Bernardo P
Baxter Healthcare Corporation, Round Lake, IL 60073.
J Pharm Sci. 1990 Feb;79(2):124-7. doi: 10.1002/jps.2600790210.
The objective of this study was to determine whether a correlation exists between the rate of in vitro dissolution and bioavailability of levothyroxine sodium (T4) tablets. Dissolution versus time profiles for Synthroid, the Flint brand of levothyroxine sodium, and two competitors' tablets (brands A and B) were generated using an official dissolution apparatus (USP), and 0.05 M phosphate buffer (pH 7.4) as the medium. These tablets were also utilized in single-dose crossover bioavailability studies in the hypothyroid dog model (n = 6). The average areas under the serum T4 concentration versus time curve from 0 to 8 h (AUC) for Synthroid, brand A, and brand B were 8.22, 6.32, and 8.70 ng-h/mL per dose (micrograms per kg body weight), respectively. Respective peak serum concentrations (Cmax) for each tablet formulation were 1.26, 1.07, and 1.36 ng/mL per dose. The corresponding dissolution rates, expressed as t50%, were 20.5, 3.06, and 14.1 min, respectively. Data analysis indicated no correlation between dissolution kinetic parameters and the bioavailability parameters AUC and Cmax. However, a linear relationship was observed between dissolution kinetics and both the time to reach maximal serum concentration (tmax) and the observed absorption rate constant (ka).
本研究的目的是确定左甲状腺素钠（T4）片的体外溶出速率与生物利用度之间是否存在相关性。使用官方溶出装置（美国药典），以0.05M磷酸盐缓冲液（pH 7.4）为介质，生成了左旋甲状腺素钠的Flint品牌优甲乐（Synthroid）以及两个竞争品牌（品牌A和品牌B）的溶出度随时间变化曲线。这些片剂还用于甲状腺功能减退犬模型（n = 6）的单剂量交叉生物利用度研究。优甲乐、品牌A和品牌B从0至8小时血清T4浓度-时间曲线下的平均面积（AUC）分别为每剂量8.22、6.32和8.70 ng·h/mL（每千克体重微克数）。每种片剂配方的各自血清峰值浓度（Cmax）分别为每剂量1.26、1.07和1.36 ng/mL。相应的溶出速率，以t50%表示，分别为20.5、3.06和14.1分钟。数据分析表明溶出动力学参数与生物利用度参数AUC和Cmax之间无相关性。然而，观察到溶出动力学与达到最大血清浓度的时间（tmax）和观察到的吸收速率常数（ka）之间呈线性关系。
