Antal E J, Jaffe J M, Poust R I, Colaizzi J L
J Pharm Sci. 1975 Dec;64(12):2015-8. doi: 10.1002/jps.2600641229.
The bioavailability of three different brands and three different dosage forms of doxycycline was studied in normal subjects. Single doses, equivalent to 200 mg of doxycycline, were administered to six subjects in a crossover design as the innovator's intravenous solution given orally (Treatment A), the innovator's capsule product (Treatment B), a noninnovator's capsule product (Treatment C), the innovator's oral suspension product (Treatment D), and a second noninnovator's capsule product (Treatment E). All dosage forms contained doxycycline as the hyclate, except the suspension which contained the nonhyclate form. Serum levels were determined periodically over 48 hr, and cumulative urinary excretion was measured concurrently over a 120-hr collection period. No statistically significant differences were observed in any in vivo indicator of bioequivalence when the three capsule products were compared. Consequently, they were judged to be bioequivalent. When these capsule products were compared to the oral solution, no statistically significant differences were observed. However, when the capsules and the suspension were compared, statistically significant differences were found in the rate of absorption. In vitro dissolution tests were also conducted on the three brands of capsules, and times required to achieve 50% dissolution showed rank-order correlation with corresponding absorption rate constants.
在正常受试者中研究了三种不同品牌和三种不同剂型的多西环素的生物利用度。以交叉设计对六名受试者给予相当于200mg多西环素的单剂量，给药方式分别为：创新者的静脉内溶液口服给药（治疗A）、创新者的胶囊产品（治疗B）、非创新者的胶囊产品（治疗C）、创新者的口服混悬液产品（治疗D）以及第二种非创新者的胶囊产品（治疗E）。除混悬液含非氢氯酸盐形式外，所有剂型的多西环素均为氢氯酸盐。在48小时内定期测定血清水平，并在120小时的收集期内同时测量累积尿排泄量。比较三种胶囊产品时，在任何生物等效性的体内指标中均未观察到统计学上的显著差异。因此，它们被判定为生物等效。当将这些胶囊产品与口服溶液进行比较时，未观察到统计学上的显著差异。然而，当比较胶囊和混悬液时，在吸收速率方面发现了统计学上的显著差异。还对三种品牌的胶囊进行了体外溶出度试验，达到50%溶出所需的时间与相应的吸收速率常数呈等级相关。
