Use of In Vitro Dynamic Colon Model (DCM) to Inform a Physiologically Based Biopharmaceutic Model (PBBM) to Predict the In Vivo Performance of a Modified-Release Formulation of Theophylline.
Use of In Vitro Dynamic Colon Model (DCM) to Inform a Physiologically Based Biopharmaceutic Model (PBBM) to Predict the In Vivo Performance of a Modified-Release Formulation of Theophylline.
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使用体外动态结肠模型（DCM）来告知基于生理的生物制药模型（PBBM），以预测茶碱的改性释放配方的体内性能。
DOI：
10.3390/pharmaceutics15030882
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发表时间：
2023-03-09
期刊：
影响因子：
5.4
通讯作者：
Mistry N
中科院分区：
文献类型：
--
作者：
Stamatopoulos K;O'Farrell C;Simmons MJH;Batchelor HK;Mistry N
开发并实施茶碱的调释制剂（Uniphyllin Continus® 200 mg片剂）的基于生理学的生物药剂学模型（PBBM），以通过整合在生物相关的体外模型（动态结肠模型（DCM））中测量的溶出曲线来预测健康男性志愿者的药代动力学（PK）数据。200 mg片剂的上级预测值（平均绝对倍数误差（AAFE）：1.1 - 1.3（DCM）vs. 1.3 - 1.5（USP II））证明了DCM优于美国药典（USP）装置II（USP II）。使用DCM中的三种运动模式（顺行和逆行传播波，基线）获得最佳预测，其产生相似的PK特征。然而，在USP II中使用的所有搅拌速度（25、50和100 rpm）下均发生片剂的广泛侵蚀，导致体外药物释放速率增加和PK数据预测过高。使用DCM的溶出曲线无法以相同的准确度预测Uniphyllin Continus® 400 mg片剂的PK数据，这可能是由于200 mg和400 mg片剂之间的上消化道（GI）滞留时间差异所致。因此，建议将DCM用于主要释放现象发生在远端胃肠道的剂型。然而，与USP II相比，DCM再次显示出基于总体AAFE的更好性能。DCM内的区域溶出曲线目前无法整合到Simcyp®中，这可能会限制DCM的预测性。因此，需要在PBBM平台内对结肠进行进一步区室化，以解释观察到的药物分布的区域内差异。
A physiologically based biopharmaceutic model (PBBM) of a modified-release formulation of theophylline (Uniphyllin Continus® 200 mg tablet) was developed and implemented to predict the pharmacokinetic (PK) data of healthy male volunteers by integrating dissolution profiles measured in a biorelevant in vitro model: the Dynamic Colon Model (DCM). The superiority of the DCM over the United States Pharmacopeia (USP) Apparatus II (USP II) was demonstrated by the superior predictions for the 200 mg tablet (average absolute fold error (AAFE): 1.1–1.3 (DCM) vs. 1.3–1.5 (USP II). The best predictions were obtained using the three motility patterns (antegrade and retrograde propagating waves, baseline) in the DCM, which produced similar PK profiles. However, extensive erosion of the tablet occurred at all agitation speeds used in USP II (25, 50 and 100 rpm), resulting in an increased drug release rate in vitro and overpredicted PK data. The PK data of the Uniphyllin Continus® 400 mg tablet could not be predicted with the same accuracy using dissolution profiles from the DCM, which might be explained by differences in upper gastrointestinal (GI) tract residence times between the 200 and 400 mg tablets. Thus, it is recommended that the DCM be used for dosage forms in which the main release phenomena take place in the distal GI tract. However, the DCM again showed a better performance based on the overall AAFE compared to the USP II. Regional dissolution profiles within the DCM cannot currently be integrated into Simcyp®, which might limit the predictivity of the DCM. Thus, further compartmentalization of the colon within PBBM platforms is required to account for observed intra-regional differences in drug distribution.
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影响因子：
5.4
作者：
O'Farrell, Connor;Simmons, Mark J. H.;Batchelor, Hannah K.;Stamatopoulos, Konstantinos
通讯作者：
Stamatopoulos, Konstantinos
DOI：
10.1152/ajpgi.2001.280.5.g922
发表时间：
2001-05-01
影响因子：
4.5
作者：
Atuma, C;Strugala, V;Holm, L
通讯作者：
Holm, L
影响因子：
3.7
作者：
Abrahamsson, B;Pal, A;Brasseur, JG
通讯作者：
Brasseur, JG
影响因子：
7.1
作者：
CASPARY, WF
通讯作者：
CASPARY, WF
影响因子：
3.7
作者：
Lloyd, Richard S.;Hingle, Martin I.;Ambery, Claire
通讯作者：
Ambery, Claire