Abrahamsson B, Alpsten M, Bake B, Jonsson U E, Eriksson-Lepkowska M, Larsson A
Astra Hässle AB, Mölndal, Sweden.
J Control Release. 1998 Mar 31;52(3):301-10. doi: 10.1016/s0168-3659(97)00267-8.
The aim of the present study was to compare the bioavailability of nifedipine when administered as a hydrophilic matrix tablet (ER) and a push-pull osmotic pump tablet (XL) administrated after fasting, and to evaluate the effect of food for the hydrophilic matrix tablet. For this purpose, three separate studies were performed on healthy volunteers (n = 58) including gammascintigraphic monitoring of tablet erosion and localisation in the gastrointestinal tract for ER in one study. Both ER and XL provided almost constant drug delivery over 24 h, after administration under fasting conditions, and bioequivalence was obtained according to 90% confidence intervals of the difference between formulations within 80-125% for Cmax and AUC. Food significantly increased AUC for ER but no significant difference was obtained between ER and XL with food with respect to extent of bioavailability. The rate of absorption was increased to a higher degree for ER than for XL, as indicated by a Cmax which was almost twice as high for ER compared with XL. This finding was shown to be related to an increased tablet-erosion rate for ER, leading to more rapid drug release.
本研究的目的是比较空腹服用时硝苯地平作为亲水骨架片（ER）和推拉渗透泵片（XL）的生物利用度，并评估食物对亲水骨架片的影响。为此，对健康志愿者（n = 58）进行了三项独立研究，其中一项研究包括对ER在胃肠道中的片剂侵蚀和定位进行γ闪烁扫描监测。在空腹条件下给药后，ER和XL在24小时内均提供几乎恒定的药物释放，并且根据Cmax和AUC在80 - 125%范围内制剂间差异的90%置信区间获得了生物等效性。食物显著增加了ER的AUC，但在生物利用度程度方面，ER和XL在进食时无显著差异。与XL相比，ER的吸收速率增加程度更高，这表现为ER的Cmax几乎是XL的两倍。这一发现表明与ER片剂侵蚀速率增加有关，导致药物释放更快。
