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1.
Although methadone is effective in the management of acute pain, the complexity of its absorption-distribution-metabolism-excretion profile limits its use as an opioid of choice for perioperative analgesia. Because deuteration is known to improve the pharmacokinetic, pharmacodynamic and toxicological properties of some drugs, here we characterized the single dose pharmacokinetic properties and post-operative analgesic efficacy of d9-methadone.The pharmacokinetic profiles of d9-methadone and methadone administered intravenously to CD-1 male mice revealed that deuteration leads to a 5.7- and 4.4-fold increase in the area under the time-concentration curve and maximum concentration in plasma, respectively, as well as reduction in clearance (0.9 ± 0.3 L/h/kg vs 4.7 ± 0.8 L/h/kg). The lower brain-to-plasma ratio of d9-methadone compared to that of methadone (0.35 ± 0.12 vs 2.05 ± 0.62) suggested that deuteration decreases the transfer of the drug across the blood-brain barrier. The estimated LD50 value for a single intravenous dose of d9-methadone was 2.1-fold higher than that for methadone. Moreover, d9-methadone outperformed methadone in the efficacy against postoperative pain by primarily activating peripheral opioid receptors. Collectively, these data suggest that the replacement of three hydrogen atoms in three methyl groups of methadone altered its pharmacokinetic properties, improved safety, and enhanced its analgesic efficacy. 相似文献
2.
王高峰 《中国医院药学杂志》1991,11(4):155-156
本文报道青霉素配伍利多卡因后的药物动力学及生物利用度研究结果,证明利多卡因对青霉素的生物利用度无影响,且可促进青霉素的吸收,为良好的青霉素无痛溶媒,建议推广使用。 相似文献
3.
通过具体的实验数据,讨论在药代动力学实验中如何加入曲线下面积(AUC)的计算,以帮助学生理解并掌握这一概念;在实验室设置不同剂量组,给药后比较剂量与浓度是否呈等比例关系,以此加深学生对于一级动力学消除及其临床意义的理解。 相似文献
4.
薄层扫描法测定血浆中盐酸氟桂利嗪浓度及药物动力学 总被引:2,自引:0,他引:2
血浆中盐酸氟桂利嗪经硼酸缓冲液酸化后,正戊烷-异丙醇(98:2)提取其原型,加酸使成盐溶于无机相中,再加碱后用二氯甲烷提取,样品点于硅胶GF254薄层板上,以环己烷-丙酮-氯仿(9:3:5)为展开剂。氟桂利嗪在254nm紫外灯下呈紫色斑点,Rf=0.54,于CS-930薄层扫描仪上测定,λs=215nm、λg=310nm,线性范围0.3 ̄8μg,平均回收率90.02%。用此法测定了氟桂利嗪血药浓度 相似文献
5.
Akosua N.J.A. de Groot Pieter W.J. van Dongen Tom B. Vree Tom K.A.B. Eskes 《European journal of obstetrics, gynecology, and reproductive biology》1995,60(2):101-107
Objective: To study the pharmacodynamic and pharmacokinetic properties of oral and intravenous methylergometrine upon uterine motility during menstruation. Study-design: Intra-uterine pressure was measured in six volunteers with a fluid-filled sponge-tipped catheter during menstruation. Methylergometrine was given orally (0.5 mg) or intravenously (0.2 mg) in a cross-over design. Results: After intravenous administration, a fast increase of the frequency of uterine contractions and basal tone occurred with a decrease of amplitude, lasting at least 30 min. Oral administration had a late and less marked effect on uterine motility. An intravenous dose administered 24 h after an oral dose had no effect on uterine motility. Pharmacokinetic data, such as the maximum plasma concentration (Cmax), the time at which Cmax is reached (tmax) and the half-life of absorption (t1/2abs) also demonstrated large individual variations after oral administration. Conclusion: Oral administration of methylergometrine had an unpredictable and late effect on uterine motility on the menstruating uterus, probably due to an unpredictable bioavailability, in contrast with the fast and predictable effect after intravenous administration. 相似文献
6.
9名男性健康自愿受试者采用三交叉单剂口服国产氛罗沙星片剂、胶囊和进口氟罗沙星片剂各400mg的药代动力学参数比较。血、尿药浓度用HPLC检测.结果表明:体内过程符合一室模型,主要药代动力学参数分别为:AUC:82.30±14.30、81.13±8.45与83.92±14.27h·mg/L;Cmax:4.71±0.83、4.67±0.51与4.86±0.89mg/L;Tmax:1.88±0.44、1.90±0.39与1.92±0.23h;T1/2ke:11.02±0.96、10.93±0.68与10.86±0.82h;V/F(c):79.08±13.31、78.42±8.70与76.39±12.93L;Cl/F:5.00±0.98、4.98±0.52与4.88±0.73L/h。服药48h的尿中原型药排出率分别为给药量的57.4%,55.9%和60.7%。国产氧罗沙星片剂和胶囊口服后药物动力学参数与进口片剂相仿.其相对生物利用及分别为98.07%与96.68%。 相似文献
7.
高效液相色谱法测定右旋儿茶素血浆浓度及药代动力学参数 总被引:1,自引:0,他引:1
本文建立了体液中右旋儿茶素的RP-HPLC测定方法。采用C_(18)键合相硅胶为填料的固相提取柱进行样品预处理,右旋儿茶素的提取回收率为79.8%.应用二极管阵列检测器对色谱峰纯度进行鉴定。该法精密度好,方法回收率近100%,日内、日间的变异系数为2.4~5.6%,血浓69.6~1160 ng/ml范围内呈线性关系,r=0.9993。家兔静注右旋儿茶素18mg/kg,其药代动力学过程符合二室模型,分布相半衰期为0.129 h,消除相半衰期为1.19h。 相似文献
8.
The distribution kinetics of a novel potent immunosuppressant, FK-506 (FK) has been studied in comparison with cyclosporin A (CyA) both in vivo and in vitro using blood specimens. The infusion studies on FK, 5.0 mg kg-1 through the portal and femoral veins showed that the mean hepatic extraction ratio of FK was 27.9 per cent. The effect of clamping both the hepatic artery and the portal vein on the plasma disappearance profiles of FK, 5.0 mg kg-1, and CyA, 3.5 mg kg-1 was studied. The plasma disposition kinetics of CyA was almost the same as in the normal rats. However, the plasma FK levels were about 10 times higher than those obtained in the control group rats. This difference is attributed to the restricted initial distribution of FK to the liver, because the volume of the initial distribution space, V1, of FK was about 10 times smaller than that obtained in normal rats. In in vitro experiments, drug distribution was studied in blood samples (2.0 ml) spiked with FK or CyA, 1.0 micrograms ml-1. The plasma drug levels measured at 2 min after drug administration were 0.842 +/- 0.012 micrograms ml-1 and 0.769 +/- 0.047 micrograms ml-1 for FK and CyA, respectively. The distribution volume in the blood compartment, VB, was determined by dividing the spiked amount of drugs with these plasma concentrations. The VB was 2.38 +/- 0.04 ml for FK and 2.62 +/- 0.16 ml for CyA. There was no significant difference in VB between FK and CyA. The plasma free fraction, fp of the drugs was measured by the equilibrium dialysis method. For FK, the mean fp values (+/- SE) were 1.31 +/- 0.18 per cent (2.0 micrograms ml-1) and 1.93 +/- 0.18 per cent (5.0 micrograms ml-1). For CyA, the fp values were 4.85 +/- 0.36 per cent (1.0 micrograms ml-1) and 5.75 +/- 0.82 per cent (5.0 micrograms ml-1). The hydrophobicity parameter, logP' determined through the HPLC method was 0.386 for FK and 0.545 for CyA. Although FK was less hydrophobic than CyA, its protein binding was higher than CyA. 相似文献
9.
Eberhard Unsöld Christian Ell Dieter Jocham Ronald Sroka Susanne Stocker 《Lasers in medical science》1990,5(3):309-316
Eight commercially available HPD-photosensitizers intended for photodynamic therapy were tested in a murine tumour model with regard to their therapeutic efficacy. The regrowth delay of the fibrosarcoma SSK-2 on the mouse C3H, Neuherberg-line, was determined 3, 24, 48 and 72 h after injection of the drugs (dose: 9 mg kg–1 body weight). The corresponding pharmacodynamics, as measured by regrowth delay, were approximated by an exponential function and the characterizing coefficients derived. These coefficients served to quantify the photodynamic properties of the drugs.The pharmacodynamics of five substances were compared with those obtained fluorometrically. The latter showed shorter decay constants than the therapy-correlated substances which indicates different metabolic behaviour of the therapeutic and diagnostically useful fluorescent components of haematoporphyrin-derived photosensitizers. 相似文献
10.
Inge Van de Walle Karen Silence Kevin Budding Liesbeth Van de Ven Kim Dijkxhoorn Elisabeth de Zeeuw Cafer Yildiz Sofie Gabriels Jean-Michel Percier Johanna Wildemann Jan Meeldijk Peter J. Simons Louis Boon Linda Cox Rob Holgate Rolf Urbanus Henny G. Otten Jeanette H.W. Leusen Peter Boross 《The Journal of allergy and clinical immunology》2021,147(4):1420-1429.e7