For establishing a precise system for predicting in vivo bioavailability following intranasal (IN) administration, the relationships among membrane permeability of drugs across Calu-3 cells, in situ nasal mucosal drug permeation rate, and in vivo drug absorption following IN administration were quantified. The membrane permeability coefficient (Papp) was determined for sixteen model drugs by in vitro permeation studies in Calu-3 cells. The drug permeation rate constant through the nasal mucosa (kn) was calculated from the in situ nasal perfusion of the drug solutions in rats. Bioavailability following IN administration of six model drugs with different membrane permeabilities were determined by in vivo drug absorption studies in rats. The correlations among in vitro membrane permeability properties, in situ nasal mucosal drug permeation rate, and in vivo drug absorption following IN administration, were assessed. The significant correlation between the in vitro Calu-3 cell permeability and nasal mucosal drug permeation rate (r2=0.812, p<0.001) indicated that nasal mucosal drug permeability is estimable from in vitro membrane permeability. Furthermore, bioavailability following IN administration significantly correlated with the in vitro Papp across Calu-3 cells (r2=0.984, p<0.001), suggesting that in vivo drug absorption following IN administration can be predicted from in vitro Calu-3 membrane permeability.

中文翻译：

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使用跨Calu-3细胞层的体外膜通透性定量估计通过鼻粘膜的药物渗透，以预测对大鼠鼻内给药后的体内生物利用度。

为了建立精确的系统以预测鼻内（IN）给药后的体内生物利用度，量化了药物跨Calu-3细胞的膜通透性，鼻腔黏膜药物透过率和IN给药后体内药物吸收之间的关系。通过在Calu-3细胞中进行体外渗透研究，确定了16种模型药物的膜渗透系数（Papp）。从大鼠药物溶液的原位鼻腔灌注计算通过鼻粘膜（kn）的药物渗透速率常数。通过大鼠体内药物吸收研究，确定了六种具有不同膜通透性的模型药物IN给药后的生物利用度。体外膜通透性，原位鼻黏膜药物渗透率，评估IN给药后的体内吸收和体内药物吸收。体外Calu-3细胞通透性与鼻粘膜药物渗透率之间存在显着相关性（r2 = 0.812，p <0.001），表明鼻粘膜药物渗透性可通过体外膜渗透性来估计。此外，IN给药后的生物利用度与跨Calu-3细胞的体外Papp显着相关（r2 = 0.984，p <0.001），表明从IN给药后的体内药物吸收可从体外Calu-3膜的渗透性预测。001）表明鼻粘膜药物的渗透性可以通过体外膜的渗透性来估计。此外，IN给药后的生物利用度与跨Calu-3细胞的体外Papp显着相关（r2 = 0.984，p <0.001），表明从IN给药后的体内药物吸收可从体外Calu-3膜的渗透性预测。001）表明鼻粘膜药物的渗透性可以通过体外膜的渗透性来估计。此外，IN给药后的生物利用度与跨Calu-3细胞的体外Papp显着相关（r2 = 0.984，p <0.001），这表明从IN给药后的体内药物吸收可通过体外Calu-3膜的渗透性来预测。