Huynh-Ngoc T, Chabot M, Sirois G
J Pharm Sci. 1978 Oct;67(10):1456-9. doi: 10.1002/jps.2600671035.
The bioavailability of three quinidine formulations was estimated during a dosing interval at steady state following their administration in 12 selected patients in accordance with a Latin-square 3 x 3. Each subject received the three dosage forms as two tablets every 12 hr for 6 days. Blood and urine samples were taken on the 7th day during the regular 12-hr dosing interval. Unchanged quinidine was determined by a reported spectrofluorometric procedure. The total fluorescence of plasma quinidine and metabolites also was monitored. The data obtained indicate that one dosage form gave a high peak level followed by a fall in the concentration. The two other forms presented a relatively lower peak followed by a plateau and then a decline. The differences between the dose-corrected values of Cp,max were statistically significant. Secondary effects were observed particularly with one dosage form and could be related to the high Cp,max value and/or the high percentage of quinidine liberated rapidly in the GI tract. Blood and urinary data indicated an equivalent degree of absorption. The dissolution behavior of the formulations and their absorption data suggest that there is a correlation between the quantity dissolved at 30 min and Cp,max.
在12名选定患者中,按照3×3拉丁方设计给药后,在稳态下的一个给药间隔期间估算了三种奎尼丁制剂的生物利用度。每位受试者每12小时服用两片这三种剂型,共服用6天。在第7天的常规12小时给药间隔期间采集血样和尿样。采用已报道的荧光分光光度法测定未代谢的奎尼丁。还监测了血浆中奎尼丁及其代谢产物的总荧光。获得的数据表明,一种剂型的血药浓度峰值较高,随后浓度下降。另外两种剂型的血药浓度峰值相对较低,随后出现平台期,然后下降。剂量校正后的Cmax值之间的差异具有统计学意义。尤其在一种剂型中观察到了次要效应,这可能与较高的Cmax值和/或在胃肠道中快速释放的奎尼丁的高百分比有关。血液和尿液数据表明吸收程度相当。制剂的溶出行为及其吸收数据表明,30分钟时的溶出量与Cmax之间存在相关性。