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首页> 外文期刊>Journal of pharmacokinetics and biopharmaceutics >In vivo evaluation of the absorption and gastrointestinal transit of avitriptan in fed and fasted subjects using gamma scintigraphy.
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In vivo evaluation of the absorption and gastrointestinal transit of avitriptan in fed and fasted subjects using gamma scintigraphy.

机译：使用伽玛闪烁显像技术在进食和禁食受试者体内评估阿维曲坦的吸收和胃肠道转运。

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The study was conducted to assess the bioavailability of avitriptan after a standard high fat meal, in relation to gastrointestinal transit. Six healthy male subjects were enrolled in a four-period study with a partial replicate design where each was administered 150-mg avitriptan capsule (i) after an overnight fast, (ii) 5 min after a standard high-fat breakfast, and (iii) 4 hr after a standard high fat breakfast. The treatment administered in Period 3 was repeated in Period 4 to assess intrasubject variations in pharmacokinetics and gastrointestinal (GI) transit. Avitriptan capsules were specially formulated with nonradioactive samarium chloride hexahydrate which was neutron-activated to gamma-emitting samarium before dosing. Serial blood samples were collected for analysis of avitriptan up to 24-hr postdose, and serial scintigraphic images were obtained to assess the plasma concentration-time profile in relation to the GI transit of the avitriptan capsule contents. Bioavailability of avitriptan was reduced when administered in the fed condition but only the decrease in AUC(INF) was statistically significant. Tmax was significantly delayed between the fed conditions and the fasted condition. Qualitative appearance of plasma concentration-time profiles for avitriptan could be related to the manner in which the drug emptied from the stomach. It was also apparent that avitriptan exerted a secondary pharmacologic effect that temporarily suspended gastric emptying in the fasted treatment. Thus, when gastric emptying was interrupted and then resumed, the net result was a double peak in some of the individual plasma concentration profiles. Scintigraphic analysis also demonstrated that upon emptying from the stomach, avitriptan was rapidly absorbed from the upper small intestine. In the fed state, gastric emptying was slow and continuous resulting in extended absorption and a lower occurrence of double peaks. Qualitatively, the intrasubject variability in Cmax and AUC could be explained by the intrasubject variability in gastric emptying in both fasted and fed conditions.
机译：进行该研究以评估阿维曲普坦在高脂餐后与胃肠道运输有关的生物利用度。六名健康男性受试者参加了为期四天的局部复制设计研究，其中每人在禁食过夜后，（ii）在标准高脂早餐后5分钟服用150毫克的阿维曲坦胶囊（ii） ）在标准的高脂早餐后4小时。在第3阶段重复进行第3阶段的治疗，以评估受试者体内药物动力学和胃肠道（GI）转运的变化。阿维曲普坦胶囊是用非放射性六氯化hydrate水合物专门配制的，在给药前经中子活化成发射γ射线的sa。收集连续血样以分析给药后24小时的阿维曲普坦，并获得连续闪烁扫描图像以评估与阿维曲普坦胶囊内容物的GI传递有关的血浆浓度-时间曲线。在饲喂条件下给药时，avitriptan的生物利用度降低，但只有AUC（INF）的降低具有统计学意义。 Tmax在进食状态和禁食状态之间显着延迟。阿维曲普坦血浆浓度-时间曲线的定性表现可能与药物从胃排空的方式有关。同样明显的是，阿维曲普坦具有第二种药理作用，可以在禁食时暂时中止胃排空。因此，当胃排空被中断然后又恢复时，最终结果是某些个别血浆浓度曲线中出现了一个双峰。闪烁扫描分析还表明，从胃排空时，阿维曲普坦从小肠上部迅速吸收。在进食状态下，胃排空缓慢而连续，导致吸收延长，双峰发生率降低。定性地，在禁食和进食条件下，受试者体内Cmax和AUC的变异性可以通过胃排空的受试者内部变异性来解释。

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