Pharmacokinetic Model Analysis of Supralingual, Oral and Intravenous Deliveries of Mycophenolic Acid.
Pharmacokinetic Model Analysis of Supralingual, Oral and Intravenous Deliveries of Mycophenolic Acid.
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舌上、口服和静脉给药霉酚酸的药代动力学模型分析。
DOI：
10.3390/pharmaceutics13040574
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发表时间：
2021-04-17
期刊：
影响因子：
5.4
通讯作者：
Xie H
中科院分区：
文献类型：
--
作者：
Gao X;Wu L;Tsai RYL;Ma J;Liu X;Chow DS;Liang D;Xie H
霉酚酸（MPA）是临床上常用的预防器官排斥反应的口服药物。最近的研究表明，MPA也具有抗癌活性。为了探索口腔癌前病变/癌性病变的新治疗选择，MPA被设计为通过粘膜粘附贴片在舌背表面局部释放。本研究的目的是建立大鼠舌上给药后粘膜粘附MPA贴剂制剂的药代动力学（PK）和舌组织分布，并比较MPA经口、静脉和舌上给药之间的PK差异。采集Sprague道利大鼠单次静脉推注、单次口服给药或舌背表面粘膜贴敷给药4 h前后的血样，所有给药剂量均为0.5 mg/kg MPA。绘制MPA血药浓度-时间曲线。由于在所有三条曲线中均发现多个峰，因此采用Phoenix软件中的肠肝循环（EHR）模型，以个体PK分析方法描述其PK参数。静脉和口服给药的平均半衰期分别为10.5 h和7.4 h。口服和舌上给药后的估计生物利用度分别为72.4%和7.6%。舌上给药后有0.5h的滞后期。结果表明，全身血浆MPA浓度低得多，在接受舌上给药的大鼠相比，从其他两种途径的剂量，和量的MPA累积在舌贴片应用后显示出持续的药物释放模式。舌上给药后舌内药物滞留动力学研究表明，揭除贴剂后约3.8%的剂量在舌内蓄积，20 h后约0.11%的剂量残留，贴敷4 h后约20.6%的MPA未从贴剂中释放。数据表明，MPA贴剂的舌上应用可以在给药部位递送大量药物，而全身循环暴露很少，因此降低了与口服给药相关的潜在胃肠道副作用。因此，舌上给药是治疗口腔病变的潜在替代途径。
Mycophenolic acid (MPA) is commonly used for organ rejection prophylaxis via oral administration in the clinic. Recent studies have shown that MPA also has anticancer activities. To explore new therapeutic options for oral precancerous/cancerous lesions, MPA was designed to release topically on the dorsal tongue surface via a mucoadhesive patch. The objective of this study was to establish the pharmacokinetic (PK) and tongue tissue distribution of mucoadhesive MPA patch formulation after supralingual administration in rats and also compare the PK differences between oral, intravenous, and supralingual administration of MPA. Blood samples were collected from Sprague Dawley rats before and after a single intravenous bolus injection, a single oral dose, or a mucoadhesive patch administration on the dorsal tongue surface for 4 h, all with a dose of 0.5 mg/kg of MPA. Plots of MPA plasma concentration versus time were obtained. As multiple peaks were found in all three curves, the enterohepatic recycling (EHR) model in the Phoenix software was adapted to describe their PK parameters with an individual PK analysis method. The mean half-lives of intravenous and oral administrations were 10.5 h and 7.4 h, respectively. The estimated bioavailability after oral and supralingual administration was 72.4% and 7.6%, respectively. There was a 0.5 h lag-time presented after supralingual administration. The results suggest that the systemic plasma MPA concentrations were much lower in rats receiving supralingual administration compared to those receiving doses from the other two routes, and the amount of MPA accumulated in the tongue after patch application showed a sustained drug release pattern. Studies on the dynamic of drug retention in the tongue after supralingual administration showed that ~3.8% of the dose was accumulated inside of tongue right after the patch removal, ~0.11% of the dose remained after 20 h, and ~20.6% of MPA was not released from the patches 4 h after application. The data demonstrate that supralingual application of an MPA patch can deliver a high amount of drug at the site of administration with little systemic circulation exposure, hence lowering the potential gastrointestinal side effects associated with oral administration. Thus, supralingual administration is a potential alternative route for treating oral lesions.
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影响因子：
3.7
作者：
Desai, Kashappa-Goud H.;Mallery, Susan R.;Holpuch, Andrew S.;Schwendeman, Steven P.
通讯作者：
Schwendeman, Steven P.
影响因子：
3.4
作者：
Jiao, Zheng;Ding, Jun-jie;Lu, Wei-yue
通讯作者：
Lu, Wei-yue
DOI：
10.2215/cjn.02820707
发表时间：
2007-11-01
影响因子：
9.8
作者：
Cattaneo, Dario;Cortinovis, Monica;Perico, Norberto
通讯作者：
Perico, Norberto
影响因子：
3.4
作者：
Dong, Min;Fukuda, Tsuyoshi;Vinks, Alexander A.
通讯作者：
Vinks, Alexander A.
DOI：
10.1515/jpem-2014-0019
发表时间：
2015-01
期刊：
Journal of pediatric endocrinology & metabolism : JPEM
影响因子：
--
作者：
Choudhary A;Sriphrapradang C;Refetoff S;Antal Z
通讯作者：
Antal Z