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991.
Y Sonoda H Yashige H Fujii S Tsuda T Maekawa S Misawa T Abe 《European journal of haematology》1992,48(1):41-48
5 patients with refractory aplastic anemia (AA) received long-term administration (2-11 + months) of recombinant human G-CSF (rhG-CSF) in doses from 250-500 micrograms/body/day by intravenous infusion or 75-300 micrograms/body/d by subcutaneous injection. All 5 evaluable patients showed a substantial increase in absolute neutrophil count (ANC) with a recovery of myeloid components in the bone marrow after 1 to 2 months of treatment. Interestingly, 2 out of the 5 patients showed a dramatic improvement in severe anemia after 2 to 4 months of treatment accompanying a recovery of erythroid components in the bone marrow. In addition, there was no serious infection before or during therapy. Long-term administration of rhG-CSF was well tolerated because of its minimal toxicity. Clonal assay revealed a recovery of myeloid progenitors in all patients and a recovery of erythroid progenitors in 3 out of the 5 patients. These results suggest that long-term administration of rhG-CSF at least mobilizes residual myeloid as well as erythroid progenitor cells and induces a bilineage response in severe refractory AA. 相似文献
992.
I Eidemak M O Friedberg S D Ladefoged H L?kkegaard E Pedersen M Skielboe 《Nephrology, dialysis, transplantation》1992,7(6):526-529
The most effective route of administration of rHuEpo is still a matter of discussion. Prospectively we studied subcutaneous (s.c.) versus intravenous (i.v.) administration in three comparable groups of patients; HD-s.c. (n = 9), HD-i.v. (n = 11), and CAPD-s.c. (n = 9). All the groups initially received 50 units/kg three times weekly. During the first 8 weeks dose adjustments were made only if target haemoglobin exceeded 11.3 g/dl (7 mM). Target haemoglobin was reached after 84 (42-98) days in the i.v. group and 42 (14-77) and 42 (28-56) respectively in the HD-s.c. and CAPD groups. The difference was statistically significant (P less than 0.05). Even the cumulative doses to reach target haemoglobin were significantly less in the two s.c. groups. To maintain haemoglobin at about 11.3 g/dl, weekly doses were as follows: HD-i.v. 125 U/kg (86-168), HD-s.c. 63 U/kg (20-85), and CAPD 72 U/kg (31-100). The total observation time after the target haemoglobin level was reached, was median 130 (114-264) days. The difference between the i.v. group and the two s.c. groups was statistically significant, (P less than 0.05) whereas there was no difference between the s.c. groups. We conclude that s.c. administration of rHuEpo is more effective in induction as well as in maintenance therapy and that s.c. administration is equally efficient in HD and CAPD patients. 相似文献
993.
F. Coudoré J. Fialip A. Eschalier and J. Lavarenne 《Fundamental & clinical pharmacology》1994,8(6):525-531
Summary— Kinetics of amitriptyline (AMI), its demethylated metabolites nortriptyline (NOR) and demethylnortriptyline (DM-NOR), and its hydroxylated metabolites, the E and Z isomers or 10-hydroxy-amitriptyline (E- and Z-10-OH-AMI) and of 10-hydroxynortriptyline (E- and Z-10-OH-NOR) were studied in plasma and brain from Swiss CD1 mice after six successive intraperitoneal injections of amitriptyline (10 mg/kg) administered every elimination half-life time (t1/2 = 3.1 h) to obtain the steady state. In these conditions, AMI was metabolised rapidly. Compared with acute administration, hydroxylation reactions were saturated by the repeated AMI injections and demethylation became preponderant both in plasma and brain. Thus, plasma levels of demethylated metabolites, NOR and DM-NOR, increased (49% and 13% of total AUC against 22% and 7% in acute conditions, respectively), while levels of AMI and its hydroxylated metabolites, 10-OH-AMI and 10-OH-NOR, decreased (8%, 2.5% and 27.5% against 17%, 8% and 46% in acute conditions, respectively). Likewise in brain tissue, when AMI was repeatedly administered, NOR and DM-NOR increased (62% and 22% against 29% and 11%, respectively) while AMI and 10-OH-AMI decreased (11.5% and 1% against 47% and 9%, respectively). These differences may account for modified pharmacological effects seen after half-life repeated administration of AMI since demethylated metabolites exert a more marked inhibiting effect than AMI on noradrenaline reuptake. 相似文献
994.
时辰药理学与合理用药 总被引:1,自引:0,他引:1
参考有关文献和资料,结合,临床用药,论述时辰药理学与人体生物节律的关系,为临床选择最佳用药时间提供参考。 相似文献
995.
Schedule dependent inhibition of thymidylate synthase (TS) and tumor growth by 5-fluorouracil (FUra) was examined in Yoshida sarcoma (YS) bearing Donryu rats. After implantation of YS cells (1 x 10(4), FUra (20 mg/kg/day) was continuously (group C) or daily bolus injection (group B) administered for 6 days. On day 7, tumor weight was 1.57 +/- 0.58 g in group C and 0.45 +/- 0.10 g in group B (P less than 0.01), free TS was 2.23 +/- 83 fmol/mg protein in group B and 96 +/- 55 fmol/mg protein in group C (P less than 0.05), and inhibition rate of TS was 88.3 +/- 5.3% in group C and 94.7 +/- 3.0% in group B (P less than 0.05). A significant correlationship was found between free TS and tumor weight (P less than 0.05). As the next step, continuous infusion (group C) or daily bolus injection (group B) for 6 days was started on day 5 after implantation of YS cells. The relative increase of tumor on day 9 was 256 +/- 111% in group C and 112 +/- 22.1% in group B (P less than 0.05). On day 11, total TS of the resected tumor was 650 +/- 153 fmol/mg protein in group C and 391 +/- 124 fmol/mg protein in group B (P less than 0.05), and inhibition rate of TS was 78.8 +/- 12.4% in group C and 84.4 +/- 8.6% in group B. Daily bolus injection of FUra causes a superior antitumor and antimetabolic effect. The schedule dependent cytotoxicity of FUra should be taken into account when a chemotherapeutic protocol is designed. 相似文献
996.
恒河猴固定比率自身给药实验动物模型的建立 总被引:1,自引:0,他引:1
本文着重研究盐酸吗啡FR1:1,4h猴自身给药实验模型的建立。结果显示,此模型潜伏期较长,但在注射次数稳定平台形成以后,踏板及注射次数客观地显示出盐酸吗啡作为强化剂能够维持猴的觅药行为,各平台注射次数之间均有显著性差异(P<0.01),但每日摄入量变化不明显。长达60d的实验,在自然戒断后,戒断症状不明显。实验表明,此精神依赖性模型的建立是成功的,且非常稳定可靠。本文还详细介绍了猴自身给药实验的手术、实验过程及维护等实验方法,为药理学工作者提供了自身给药实验的方法学参考依据。 相似文献
997.
998.
我国即将恢复关贸总协定缔约国的地位,这就迫使制药工业、药品经营重新建立起符合关贸总协定要求的运行机制。本文就“入关”前后,药品监督管理工作面临的新问题提出一些设想,为“入关”作思想上的准备。 相似文献
999.
用静脉自身给药法评价可卡因及麻黄碱的精神依赖性 总被引:1,自引:0,他引:1
本项工作采用静脉自身给药(intravenousself-administration)方法,评价可卡因(cocaine)及麻黄碱(cphcdrine)的精神依赖性。当可卡因的一次注射剂量为1.0mg·kg-1及0.5mg·kg-1时.大鼠可以在固定比率(fixedratio,FR)为1的实验程序控制下形成自身给药行为。当剂量增加时大鼠的踏板频率下降,但是药物的总摄入量没有改变。麻黄碱一次注射剂量为4.78mg·kg-1时,可以作为替代药物维持大鼠的自身给药行为。 相似文献
1000.
Summary The pharmacokinetics of verapamil in five healthy volunteers were investigated on 4 occasions during chronic administration of deuterated verapamil. There was no statistically significant difference in oral clearance, terminal half-life, bioavailability, morning trough level and peak concentration or in the time of their occurrence on the four occasions. The plasma clearance, however, exhibited considerable inter- and intra-individual variation, ranging between 26.3% and 85.4% and 12.0% and 48.0%, respectively. Comparison of these pharmacokinetic parameters with data from previous single dose studies in the same subjects revealed a significant (p<0.05) decrease in the clearance and an increase in the apparent bioavailability of verapamil during chronic administration, although no difference in the half-life was found. Due to the considerable variation in the oral clearance of verapamil during chronic dosing, steady-state conditions in a strict pharmacokinetic sense may never be attained, and pharmacokinetic data obtained in single dose studies will be of limited value in predicting steady-state plasma concentrations. 相似文献