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1.
修饰已上市药物以改善药物存在的缺陷,是目前全球药物研发的一个重要方向。以高分子前药为基础的给药系统具有前药修饰和微纳米载药的双重优势,可以增强药物在体内、体外的稳定性,增加药物的靶向性,提高药物的生物利用度、降低药物不良反应和提高治疗效果。本文根据高分子前药的研发机制,从被动靶向、主动靶向、触发释药和协同给药进行综述,探讨该类药物的研发现状及所面临的问题,并对此给出适当可行的解决方案。  相似文献   
2.
Objective: To assess the safety and efficacy of long-term administration of teneligliptin alone and in combination with oral antidiabetic drugs in Japanese type 2 diabetes mellitus (T2DM) patients with insufficient glycemic control.

Methods: This post-hoc pooled analysis used data from two Phase III clinical studies involving 702 Japanese patients. We evaluated teneligliptin as monotherapy and combined with a sulfonylurea, glinide, biguanide, or α-glucosidase inhibitor. Safety measures included adverse events (AEs), adverse reactions and hypoglycemia. The main efficacy measure was the change in glycated hemoglobin (HbA1c) from baseline.

Results: Incidences of AEs and adverse reactions were similar among the teneligliptin monotherapy group and all combination therapy groups except the combination with sulfonylurea. Hypoglycemia was more frequent in the sulfonylurea combination therapy group than in other groups. Teneligliptin administered once daily as monotherapy or combination therapy resulted in a decrease in HbA1c, which was maintained for 52 weeks. Bodyweight showed no change or a slight increase at the end of 52 weeks in all groups.

Conclusions: This pooled analysis provides evidence for the safety and efficacy of long-term use of teneligliptin as monotherapy or combination therapy in Japanese T2DM patients.  相似文献   

3.
Xing PP  Wu WH  Du P  Han FM  Chen Y 《药学学报》2011,46(5):573-580
马钱子碱每日低、中、高(3,15和60 mg·kg-1)剂量以及高剂量马钱子碱和甘草次酸(每日25 mg·kg-1)、甘草苷(每日20 mg·kg-1)配伍,分别对Wistar大鼠连续灌胃给药7天后,检测不同给药组对CYP3A、CYP1A2、CYP2E1和CYP2C的酶活性和mRNA表达的影响。与对照组相比,高剂量马钱子碱使CYP3A活性下降24.5%,CYP2C的活性下降34.6%,而使CYP2E1的活性提高了146.1%。另一方面,与高剂量组相比,甘草次酸配伍组使CYP2E1的活性降低了51.4%,CYP1A2的活性降低了33.5%;甘草苷配伍组使CYP2E1的活性降低了41.1%,CYP2C的活性降低了37.7%。实验结果表明,马钱子碱和甘草次酸、甘草苷配伍后,可以在一定程度上影响上述CYP450酶的mRNA表达和酶活性。因此推测配伍后甘草苷对马钱子碱所致CYP450酶异常变化的拮抗作用,以及甘草次酸对CYP2E1和CYP1A2活性的抑制作用,可能是甘草降低马钱子毒性的重要机制之一。  相似文献   
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中药及其制剂作为临床上重要治疗手段常与化学药物联合使用,因此,应关注中药与化学药物之间的相互作用。乳腺癌耐药蛋白(Breast Cancer Resistance Protein,BCRP)是重要的外排转运体之一,参与体内诸多药物的吸收、分布、代谢、排泄过程。BCRP的表达和外排活性常受相关底物或抑制剂影响,进而改变联合用药的药代动力学,导致药物相互作用。本文主要就银杏、姜黄、甘草、人参、黄芪等常见中药及其主要成分对BCRP的影响及其可能引起的药物相互作用进行综述,为规避临床中药-化学药物联合用药风险提供科学依据。  相似文献   
6.
The present study was designed to investigate the molecular mechanisms of NAC (150 mg/kg bw twice/week) action in vivo under repeated hCG (100 IU/rat/day) stimulation to adult rats. Leydig cell refractoriness led to a significant decline in serum testosterone and intracellular cAMP by day 30 of chronic hCG intervention which improved significantly following NAC co-administration. It inhibited the rise in lipid peroxidation, improved the activity of antioxidant enzymes along with intracellular glutathione and total antioxidant capacity in the target cells. Leydig cell apoptosis declined significantly (P < 0.001) with down-regulation of upstream, Fas, FasL, caspase-8, Bax and caspase-9, JNK/pJNK and downstream caspase-3 and PARP. On the other hand, anti-apoptotic Bcl2, NF-kβ, and Akt were up-regulated. Taken together, the above findings indicate that the specificity of NAC action was not restricted to regulating marker proteins in the extrinsic and JNK pathways as seen in vitro but extended to include intrinsic pathway of metazoan apoptosis as well.  相似文献   
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8.
目的 探讨联合给药治疗新生儿尿布皮炎对药物经皮渗透指标的影响.方法 以家兔为研究模型,分成三组,每组8只,分别进行单独应用氧化锌油、制霉菌素及两种药物联合应用的体外经皮渗透实验.测定三组经皮渗透量、渗透速率及滞后时间等渗透指标.结果 氧化锌组与混合用药组氧化锌的经皮渗透指标比较,差异无统计学意义(均P>0.05);制霉菌素组与混合用药组中制霉菌素的经皮渗透指标比较,差异有统计学意义(均P<0.01).结论 氧化锌与制霉菌素混合用药中制霉菌素的渗透率低于单一应用制霉菌素.氧化锌油与制霉菌素联合应用时应采用交叉给药,混合给药干扰制霉菌素的经皮渗透效果.  相似文献   
9.
Summary The pharmacokinetics of atenolol with and without the co-administration of chlorthalidone were studied in five hypertensive subjects. Concomitant administration of chlorthalidone appears to have little if any effect on the pharmacokinetics of atenolol during treatment for 7 days. The atenolol elimination half-lives were 6.7±1.1 and 6.3±0.9 h, respectively, with and without chlorthalidone. Two healthy volunteers also received a single 50 mg oral dose of chlorthalidone. Their blood profiles and pharmacokinetics were similar to those observed in hypertensive subjects, but a statistically significant difference (p<0.01) was found between the urinary excretion half-lives of chlorthalidone. This difference may be because chronic administration of the drug caused saturation of red cell binding.  相似文献   
10.
Summary The effect of cimetidine on the single and multiple dose pharmacokinetics of enteric coated ketoprofen was studied in 12 healthy volunteers. Each subject completed two 8-day study treatment periods: either ketoprofen alone (100 mg p.o. twice daily), or co-administered with cimetidine (600 mg twice daily). tlag, Cmax, tmax, t1/2, and k for ketoprofen were not significantly different between single and multiple dose administration. AUC of ketoprofen was slightly but significantly larger following multiple (21.2 µg·h·ml–1) as compared to single dose administration (19.0 µg·h· ml–1). As a result, plasma clearance of ketoprofen was slightly but significantly reduced following multiple dose administration (80.6 ml/min vs 89.3 ml/min). Cimetidine had no effect on the single or multiple dose pharmacokinetics of enteric coated ketoprofen. Total 12-h urinary recovery of ketoprofen (mostly in the form of ketoprofen glucuronide) was 83.5% of the dose following single dose administration and was significantly greater following multiple dose administration (93.1%). Again cimetidine co-administration had no effect on the single and multiple dose urinary recovery.The results of this study show that cimetidine is not affecting the oral pharmacokinetics of enteric coated ketoprofen.  相似文献   
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