Gao J Zh, Hussain M A, Motheram R, Gray D A B, Benedek I H, Fiske W D, Doll W J, Sandefer E, Page R C, Digenis G A
Bristol-Myers Squibb Company, Biopharmaceutics R&D, New Brunswick, New Jersey 08903-0191, USA.
J Pharm Sci. 2007 Nov;96(11):2970-7. doi: 10.1002/jps.20962.
Human pharmacoscintigraphic behavior of two tablets and a capsule formulation of a high dose, poorly water soluble, highly permeable, micronized drug (efavirenz) was investigated. The tablets and capsule, prepared with samarium oxide and neutron activated to produce radioactive samarium-153, were evaluated for their in vivo disintegration and gastrointestinal (GI) transit in healthy subjects under fasted condition. Scintigraphic images were acquired to coincide with blood sampling times to assess the plasma concentration-time profile in relation to in vivo disintegration and GI transit. The mean gastric emptying times were approximately the same for all three formulations. Although in vivo dosage form disintegration was faster for Tablet A as compared to Tablet B and was similar between Tablet A and the capsule, Tablet A showed a slower rate and extent of drug absorption than Tablet B and the capsule. The results of this study eliminated the initial hypothesis that the difference in in vivo performance between the two tablet formulations is due to a different rate of in vivo disintegration and suggest that for this drug the in vivo dissolution rate of the drug from its disintegrated dosage form was a more important factor affecting the rate and extent of drug absorption.
对一种高剂量、水溶性差、高渗透性的微粉化药物（依非韦伦）的两种片剂和一种胶囊制剂的人体药物闪烁行为进行了研究。用氧化钐制备并经中子活化以产生放射性钐 - 153的片剂和胶囊，在禁食条件下对健康受试者的体内崩解和胃肠道（GI）转运进行了评估。采集闪烁图像以与采血时间一致，以评估与体内崩解和胃肠道转运相关的血浆浓度 - 时间曲线。所有三种制剂的平均胃排空时间大致相同。尽管与片剂B相比，片剂A的体内剂型崩解更快，且片剂A与胶囊之间相似，但片剂A的药物吸收速率和程度比片剂B和胶囊慢。本研究结果排除了最初的假设，即两种片剂制剂之间体内性能的差异是由于体内崩解速率不同，并表明对于这种药物，药物从其崩解剂型的体内溶解速率是影响药物吸收速率和程度的更重要因素。
