Surampalli Gurunath, Satla Madhuchander, Nanjwade Basavaraj K, Patil Paragouda A
a Department of Pharmacology and Toxicology , Vaagdevi Institute of Pharma Sciences , Telangana, Warangal , India.
b Department of Obstetrics and Gynecology , Kakatiya Medical College , Warangal, Telangana , India.
Drug Dev Ind Pharm. 2017 May;43(5):812-829. doi: 10.1080/03639045.2016.1220569. Epub 2016 Aug 28.
In-situ evaluation to corroborate morin effects on the intestinal absorption and pharmacokinetic behavior of freeze-dried OLM-loaded solid dispersions with Caco-2 and in-vivo studies Methods: Intestinal transport and absorption studies were examined by Caco-2 permeability, in-situ single pass perfusion and closed-loop models along with in-vivo pharmacokinetic studies to evaluate and confirm the effect of P-gp-mediated activity of morin. We evaluated the intestinal membrane damage in the presence of morin by measuring the release of protein and lactate dehydrogenase (LDH) followed by using qualitative and quantitative morphometric analysis to describe the surface characteristics of intestinal epithelium.
Morin showed the highest P value 13.8 ± 0.34 × 10cm/s in jejunum than ileum (p < .01) at 100 µM with absorption enhancement of 1.31-fold together with enhanced (p < .01) secretory transport of 6.27 ± 0.27 × 10 cm/s in Caco-2 monolayer cells. Our findings noticed 2.37 (in-situ); 2.39 (in-vivo) and 1.43 (in-situ); 1.36 (in-vivo) fold increase in AUC with elevated C and shortened T for freeze-dried solid dispersion in the presence of morin as compared to pure OLM and freeze-dried solid dispersions without morin, respectively.
Our study demonstrated that increased solubilization through freeze-dried OLM-loaded solid dispersion together with efflux inhibition improved intestinal permeability to one system that might lead to novel solubilization and efflux pump inhibition as a novel alternative potential to increase oral absorption and bioavailability of OLM.
通过体外评价以证实桑色素对载有奥替拉西钾冻干固体分散体在Caco-2细胞中的肠道吸收及药代动力学行为的影响，并进行体内研究。方法：采用Caco-2细胞通透性、原位单通道灌注和闭环模型进行肠道转运和吸收研究，同时进行体内药代动力学研究，以评估和确认桑色素P-糖蛋白介导活性的作用。通过测量蛋白质和乳酸脱氢酶（LDH）的释放来评估桑色素存在时的肠膜损伤，随后使用定性和定量形态计量分析来描述肠上皮的表面特征。
在100µM时，桑色素在空肠中的P值最高，为13.8±0.34×10cm/s，高于回肠（p<0.01），吸收增强1.31倍，同时在Caco-2单层细胞中分泌转运增强（p<0.01），为6.27±0.27×10cm/s。我们的研究发现，与纯奥替拉西钾和不含桑色素的冻干固体分散体相比，在桑色素存在下，冻干固体分散体的AUC分别增加了2.37倍（体外）；2.39倍（体内）和1.43倍（体外）；1.36倍（体内），同时C升高，T缩短。
我们的研究表明，通过载有奥替拉西钾的冻干固体分散体增加溶解度以及抑制外排，可提高对某一系统的肠道通透性，这可能会产生新的增溶和外排泵抑制作用，作为提高奥替拉西钾口服吸收和生物利用度的一种新的潜在替代方法。
