喹诺酮类药物的临床应用

喹诺酮类抗菌药物是一类全合成的抗菌药物,具有抗菌谱广、抗菌力强、作用机制独特、高效、低毒等特点.新型的喹诺酮类药物更是具有生物利用度高、半衰期长、血药浓度高、组织分布广等优点,广泛用于呼吸系统、消化系统感染性疾病的治疗.但是抗菌药物的临床应用增多,其耐药问题也日益突出.如何合理使用喹诺酮类药物是临床面临的重要问题.     

Solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine for enhanced bioavailability of highly lipophilic bioactive carotenoid lutein

The objectives of this study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine (PC), an endogenous phospholipid with excellent in vivo solubilization capacity, as oil phase for the delivery of bioactive carotenoid lutein, by spray drying the SNEDDS (liquid system) containing PC using colloidal silica (Aerosil® 200 VV Pharma) as the inert solid carrier, and to evaluate the enhanced bioavailability (BA) of lutein from S-SNEDDS. The droplet size analyses revealed droplet size of less than 100 nm. The solid state characterization of S-SNEDDS by SEM, DSC, and XRPD revealed the absence of crystalline lutein in the S-SNEDDS. The bioavailability study performed in rabbits resulted in enhanced values of C_max and AUC for S-SNEDDS. The enhancement of C_max for S-SNEDDS was about 21-folds and 8-folds compared with lutein powder (LP) and commercial product (CP), respectively. The relative BA of S-SNEDDS compared with CP or LP was 2.74-folds or 11.79-folds, respectively. These results demonstrated excellent ability of S-SNEDDS containing PC as oil phase to enhance the BA of lutein in rabbits. Thus, S-SNEDDS containing PC as oil phase could be a useful lipid drug delivery system for enhancing the BA of lutein in vivo.     

健康受试者醋酸环丙孕酮片的生物等效性测定

目的:研究检测比较人体单次口服受试制剂醋酸环丙孕酮片和参比制剂醋酸环丙孕酮片的生物利用度。方法:18名男性健康志愿者采用两制剂双周期交叉试验设计,口服醋酸环丙孕酮片受试制剂和参比制剂各100mg,于不同时间采集血样,并采用高液相色谱法测定血药浓度。结果:受试者口服两种醋酸环丙孕酮片受试制剂和参比制剂后,T_(max)分别为(3.7±0.8)h和(3.9±0.5)h,C_(max)分别为(145.0±46.8)和(151.1±47.9)ng/ml,AUC0￣96分别为(2303.6±446.2)和(2182.2±426.5)ng/(h·ml)。醋酸环丙孕酮片受试制剂和参比制剂消除均较缓慢,消除半衰期分别为(29.4±10.3)和(26.4±7.4)h。AUC0￣96和C_(max)经对数转化后进行方差分析和双单侧t检验,T_(max)进行秩和检验,结果表明受试制剂的AUC0￣96、C_(max)和T_(max)与参比制剂比较差异无统计学意义。结论:醋酸环丙孕酮片受试制剂的人体相对生物利用度为(107.4±19.2)%,与参比制剂具有生物学等效性。     

单剂量口服复方氨酚烷胺胶囊在人体内的生物等效性

目的 选择18名受试者单剂量交叉po两种复方氨酚烷胺胶囊,评价其生物等效性.方法 用HPLC测定血中对乙酰氨基酚和咖啡因的药物浓度,用3p97软件计算药动学参数;用方差分析和双单侧t检验分析两种复方氨酚烷胺胶囊中对乙酰氨基酚和咖啡因的主要药动学参数.结果 对乙酰氨基酚的Tmax分别为0.99±0.47、0.88±0.39 h,Cmax分别为8.40±2.99、8.62±5.00 μg·ml-1,AUC0-24分别为35.42±9.54、33.84±10.37 mg·h·L-1;咖啡因的Tmax分别为0.94±0.24、0.90±0.19 h,Cmax分别为1.22±0.31、1.26±0.42 μg·ml-1,AUC0-24分别为8.80±2.01、8.43±2.23 mg·h·L-1.结论 两种制剂具有生物等效性.     

Pharmacokinetics of meloxicam administered as regular and fast dissolving formulations to the rat: Influence of gastrointestinal dysfunction on the relative bioavailability of two formulations

It is believed that acute pain suppresses nervus vagus, thereby, influencing gastrointestinal secretion and motility, which are the two factors that are necessary for disintegration and dissolution of solid dosage forms. We studied the pharmacokinetics of meloxicam and the effect of vagal suppression on the oral bioavailability and bioequivalence using a marketed (Brand) and a fast dissolving (FD) formulation. In simulated gastric juice, FD was disintegrated in 30 s and released 30% of its meloxicam in 15 min and 60% in 2 h. Brand was disintegrated in 4.5 min with a dissolution rate of 5.6% in 30 min that stayed plateau for the 2 h experiment time. To suppress the vagus nerve, intraperitoneal injection of 20 mg/kg propantheline 1 and 2 h before meloxicam administration was used. Meloxicam (0.9 mg/kg) was administered to both control and vagally suppressed rats i.v. (n = 4–6/group) as well as orally in a paired random fashion as broken pieces of Brand or FD tablets (n = 7/ group). Serial (0–48 h) blood samples were collected for pharmacokinetic and bioavailability studies. Relative bioavailability was measured according to a method in use for bioequivalence assessments. Systemic pharmacokinetics of meloxicam was not affected by vagal suppression. Absolute bioavailability of meloxicam, based on 0–48 h measurement, was >0.68 regardless of the type of formulation and treatment. Vagal suppression, however, significantly reduced AUC_0–24 (μg h mL⁻¹) for Brand (control, 58.8 ± 22.0 vs treated, 22.1 ± 9.7) but not for FD (control, 63.5 ± 17.9 vs treated, 64.6 ± 8.9) indicating a reduced absorption rate for the former. The peak time for Brand was also significantly delayed by over 20 h for Brand and not for FD. Relative bioavailability was confirmed between FD and Brand that were in control but not in the vagally suppressed rats, indicating a disease-dependent bioequivalence. The effect of vagal suppression on the drug absorption rate can be obviated if the disintegration and dissolution become independent of gastrointestinal motility and secretion.     

中草药在促进西药吸收和提高血药浓度方面的作用

分类综述近年来有关利用中草药及其活性成分促进西药吸收和提高血药浓度及其作用机制的研究报道。某些中草药的活性成分可以通过提高吸收性上皮细胞膜的通透性、抑制外排蛋白和代谢酶，增加西药的体内吸收和血药浓度。     

辛伐他汀片人体药代动力学及相对生物利用度的研究

目的:评价2种辛伐他汀片的相对生物利用度和生物等效性.方法:选择18名健康受试者随机分为2组,先后予单剂量、交叉口服辛伐他汀受试制剂和参比制剂各40 mg,采用液相色谱-质谱-质谱联用法测定给药后不同时间受试者血浆中辛伐他汀的浓度,对辛伐他汀受试制剂和参比制剂进行生物等效性评价.结果:辛伐他汀受试制剂和参比制剂的主要药代动力学参数:cmax分别为(9.70±6.62)及(10.06±6.29) μg/L;tmax分别为(1.64±1.01)及(1.64±0.68)h;t1/2分别为(3.48±1.16)及(4.15±1.90)h;AUC0～14h分别为(29.96±16.28)及(32.78±18.53)μg·h·L-1;AUC0～∞分别为(31.49±16.65)及(36.39±21.71) μg·h·L-1.受试制剂的相对生物利用度为(97.79±26.63)%.结论:2种制剂具有生物等效性.     

盐酸左氧氟沙星胶囊的人体生物等效性研究

目的:评价盐酸左氧氟沙星胶囊与已上市的盐酸左氧氟沙星胶囊的人体生物等效性.方法:18名健康男性志愿者双周期自身交叉单剂量口服受试药物和参比药物各200 mg,采用高效液相色谱-荧光检测法测定血清中药物浓度,用DAS软件计算药代动力学参数和相对生物利用度,并进行生物等效性评价.结果:盐酸左氧氟沙星胶囊的受试药物与参比药物的Cmax分别为(3.206±0.498)μg/ml、(3.255±0.436)μg/ml;tmax分别为(0.931±0.307)h、(0.903±0.322)h;AUC0～36分别为(23.780±4.986)(μg·h)/ml、(23.934±5.625)(μg·h)/ml;AUC0～∞分别为(24.510±5.189)(μg·h)/ml、(24.684±5.973)(μg·h)/ml;受试药物的相对生物利用度为(103.9±29.1)%.结论:经统计学分析,两种盐酸左氧氟沙星胶囊具有生物等效性.     

口服促肝细胞生长素微球在大鼠体内的药代动力学和生物利用度

目的研究促肝细胞生长素微球在大鼠体内的药代动力学和生物利用度。方法用高效液相色谱测定大鼠血中促肝细胞生长素浓度，3P97程序计算参数。结果促肝细胞生长素微球的药动学参数分别：Cmax=（28．60±9．43）μg／ml，tmax=210min，t1／2（β）=（144．40±19．78）min，AUG0-∞=（7662．03±704．36）μg·min／ml，相对于胶囊剂内容物的生物利用度是238．8％。结论大鼠对促肝细胞生长素微球的吸收明显优于胶囊剂内容物。     

阿奇霉素片的相对生物利用度和生物等效性

目的:考察阿奇霉素片人体相对生物利用度及生物等效性。方法:22名健康男性志愿者,采用交叉给药方案,分别单剂量口服20mg受试阿奇霉素片和参比阿奇霉素片,用液相色谱-串联质谱法测定血浆中阿奇霉素浓度,进行人体相对生物利用度和生物等效性评价。结果:单次口服20mg受试阿奇霉素片和参比阿奇霉素片后,达峰时间Tmax分别为(2.0±1.4)h和(1.8±0.6)h;峰值血药浓度Cmax分别为(584.27±258.93)ng/ml和(523.27±186.53)ng/ml;t1/2分别为(47.64±10.38)h和(51.96±12.49)h;药时曲线下面积采用梯形法计算,AUC0→t分别为(3532.26±1311.69)和(3500.10±1229.70)ng.h/ml,AUC0→∞分别为(3986.30±1443.53)ng.h/ml和(4015.14±1426.56)ng.h/ml。结论:国产阿奇霉素片的相对生物利用度为(104.3±27.8%),主要参数的双单侧t检验,结果显示两种制剂为生物等效制剂。