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21.
目的 观察卡铂碳包铁纳米笼壳聚糖微球 ( carboplatin-Fe@C-loaded chitosan nanoparticles , C - Fe@C-CN )结合磁场在移植性肝癌大鼠模型体内的靶向分布情况和药动学过程。 方法 建立移植性肝癌大鼠模型 40 只为 A 组, 正中开腹行肝动脉插管,按卡铂 5 mg·kg-1 体重注入 C-Fe@C-CN 的生理盐水分散液,以肿瘤组织为靶区施加 0.5 T 磁场 30 min 。分别在给药后 0.25 , 0.5 , 1 , 3 , 6 , 12 , 24 和 48 h 各时间点,每组取 5 只大鼠处死,采集血浆、靶区肿瘤、非靶区肝、肾、脾和肺组织标本,石墨炉原子分光光度计测定血浆和组织中卡铂浓度,药物浓度数据用 3P87 药动学程序分析处理,并组织学 观察 C-Fe@C-CN 的在各脏器分布情况。 另 40 只健康大鼠为 B 组,以左肝叶为靶区,给予相同的处理作为对照。 结果 A 组靶区肿瘤组织 <> c max 是 65.21 μg·g-1 ,为 B 组靶区肝组织( 38.47 μg·g-1 )的 1.7 倍。 48 h 时 A 组靶区肿瘤组织药物浓度是 7.27 μg·g-1 ,为 B 组靶区肝组织( 3.11 μg·g-1 )的 2.3 倍。 A 组靶区肿瘤组织 AUC 是 906 mg·h·L-1 ,为 B 组靶区肝组织( 421.34 mg·h·L-1 )的 2.2 倍。 2 组药动学参数值相近。病理学观察 显示, C-Fe@C-CN 在磁场作用下聚集于肿瘤细胞间隙中,并可栓塞于部分细小动脉。非靶区肝组织内少见 C-Fe@C-CN 的聚集和栓塞的血管。 结论 C-Fe@C-CN 在体内具有长循环和缓释特性,在磁场的引导下对肿瘤组织具有更强的靶向性,成倍提高肿瘤组织中的药物浓度,延长维持时间。 相似文献
22.
用放射免疫法(RIA)测定甲地孕酮(MA)血清浓度并计算了在家兔和大鼠静注或口服的药物动力学参数。MA口服的生物利用度,家兔为64%,大鼠为56%。MA肝微粒体酶代谢实验提示有极性较MA为大的代谢产物形成,~3H-MA十二指肠给药后30min内门静脉血中放射性远高于外周血,也有极性代谢产物形成。 相似文献
23.
24.
Tacrolimus Exposure and Evolution of Renal Allograft Histology in the First Year After Transplantation 总被引:1,自引:1,他引:0
M. Naesens E. Lerut B. V. Damme Y. Vanrenterghem D. R. J. Kuypers 《American journal of transplantation》2007,7(9):2114-2123
Tacrolimus has a narrow therapeutic window and is characterized by a large inter-individual variability in bioavailability. The impact of tacrolimus exposure on subclinical evolution of graft histology has not been studied in renal recipients. This analysis included 239 protocol biopsies (obtained at implantation, 3 and 12 months) of 120 consecutive kidney recipients treated with tacrolimus, mycophenolate mofetil (MMF) and corticosteroids. Biopsies were scored according to the Banff 2001 criteria and a chronicity score was calculated. Prospective pharmacokinetic data were included in the analysis (5544 tacrolimus predose blood concentrations and tacrolimus AUC(0-12) at 3 and 12 months). Higher donor age and higher number of human leukocyte antigen-DR (HLA-DR) mismatches were independent predictors of subclinical acute rejection at 3 months, present in 8.7% of patients. The number of HLA-DR mismatches was independently associated with biopsy-proven clinical acute rejection. Biopsy-proven acute rejection episodes and low mean tacrolimus exposure were independently associated with higher increase in chronicity scores between 3 and 12 months after transplantation. This observational study suggests that rejection phenomena and immune-mediated mechanisms remain important in the early progression of chronic allograft pathology. Tacrolimus doses or systemic exposure were not associated with lesions of calcineurin inhibitor nephrotoxicity, suggesting that other factors determine susceptibility to tacrolimus nephrotoxicity. 相似文献
25.
26.
目的研究在离体模式下地氟醚、异氟醚和氟烷通过氧合器应用的药代动力学。方法选择成人型膜式氧合器,预充生理盐水2000ml,连接动静脉端形成环路。将预先配制在钢瓶内的2.4%地氟醚、0.46%异氟醚及0.308%氟烷混合气体输送至氧合器,气体流量3Umin,泵流量4Umin,温度30℃。在摄入及排出的0、1、2、4、8、16、32min采集氧合器入气口、排气口及动脉端样本,测定吸入麻醉药分压。结果在摄入阶段及排出阶段,动脉端溶液中三种吸入麻醉药分压迅速上升或下降,用药后8min时,三种药物的动脉端样本分压与吸入气分压之比(Pa/Pi)均达50%以上,停药后8min动脉端样本分压与动脉端样本分压峰值之比(Pa/Pa0)均降至10%以下。三种药物之间在同一时间点Pa/Pi及Pa/17aO均有显著性差异(P<0.05)。各吸入麻醉药动脉端样本与氧合器排气口中分压之间呈线性相关关系(r=0.99)。结论(1)Bentley膜式氧合器具有快速转运吸入麻醉药的性能;(2)地氟醚、异氟醚及氟烷通过氧合器应用后摄取和排出速率随着药物的水/气分配系数的增高而减慢;(3)通过监测氧合器排气口中吸入麻醉药分压可以快速、准确地估计液相中吸入麻醉药分压。 相似文献
27.
Betlach Charles J. Arnold John D. Frost R. Wayne Leese Philip T. Gonzalez Mario A. 《Pharmaceutical research》1987,4(5):409-411
The bioavailability of a new sustained-release potassium chloride (KC1) tablet, designed for once-a-day dosing, was compared to a KC1 elixir using urinary excretion data. The study utilized 25 male volunteers dosed in a crossover design in a dietary/activity-controlled environment. The regimens consisted of a total of 80 mEq of potassium in three equally divided doses of elixir every 6 hr and a single 80-mEq dose using four 20-mEq sustained-release (SR) tablets. The mean time to maximum rate of potassium urinary excretion was 2.2 hr for the first elixir dose and 5.5 hr after the SR tablet (P < 0.01), thereby supporting the prolonged-release properties of this formulation. After correction for baseline urinary potassium excretion, the mean total 24-hr urinary potassium excretion was 42.18 mEq for the elixir and 40.41 mEq for the SR tablet. The results indicate that the absorption pattern from the SR tablet is equal to three doses of KC1 elixir dosed 6 hr apart. 相似文献
28.
通过8名健康志愿者服药后的对照实验,用微生物法检测血药浓度,按一室模型配置求算药物动力学参数,探讨西咪替丁对林可霉素体内过程的影响。结果表明,西咪替丁不能改变林可霉素的吸收速率(Ka)和消除速率(Ke),但可通过增加其吸收程度或改变其分布容积,使林可霉素的血药浓度和生物利用度分别增加约19%和27%。 相似文献
29.
Robert B. Forbes David J. Murray Judith B. Dillman David L. Dull 《Journal canadien d'anesthésie》1989,36(2):160-164
Plasma methohexitone concentrations were determined in 60 children, aged one to six years, following administration of 15 mg.kg-1, 20 mg.kg-1, 25 mg.kg-1 or 30 mg.kg-1 two per cent rectal methohexitone. Time to the onset of sleep was determined by a blinded observer and venous blood samples obtained 15, 30, 45 and 120 minutes following drug administration. Fifty of 60 children were asleep within 15 minutes. Nine of the ten children that did not fall asleep were sedate and could be separated easily from their parents to undergo inhalational induction of anesthesia. Time to the onset of sleep was inversely related to the dose of rectal methohexitone administered. Sleep was achieved more reliably following the use of 25 to 30 mg.kg-1 rectal methohexitone. In addition, plasma methohexitone concentrations following 30 mg.kg-1 rectal methohexitone were significantly higher for up to 120 minutes following drug administration than the plasma concentrations achieved after 15 mg.kg-1 or 20 mg.kg-1 methohexitone. There was no difference in the incidence of complications. The authors recommend that clinical circumstances be carefully considered and the dose of rectal methohexitone administered be individualized to meet the specific anaesthetic requirements of each child. 相似文献
30.
E. Perucca R. Grimaldi G. Ruberto C. Gelmi F. Trimarchi A. Crema 《European journal of clinical pharmacology》1986,29(6):729-730
Summary The kinetics of phenobarbital (PB) was compared after oral administration of equivalent doses of the drug as the acid or the propylhexedrine salt (barbexaclone) to 7 normal volunteers. The absorption and elimination parameters were very similar. It was concluded that propylhexedrine did not affect the serum kinetics of PB given as barbexaclone. 相似文献