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91.
F Elferink W J van der Vijgh W W ten Bokkel Huinink J B Vermorken I Klein B Winograd M K Knobf G Simonetti H E Gall J G McVie 《British journal of cancer》1987,56(4):479-483
Pharmacokinetics of the cis-platin analog ethylenediaminemalonatoplatinum(II) (JM-410) was studied in 28 cycles of 19 patients during the phase I study of this drug. The drug was administered intravenously by short-term (10-60 min) infusion. Doses ranged from 20 to 1,200mg m-2. JM-40 was determined in plasma ultrafiltrate and urine by HPLC. Platinum (Pt) concentrations were determined in plasma, plasma ultrafiltrate, urine and red blood cells by atomic absorption spectrometry up to 5 days after administration of the drug. Ultrafilterable Pt could be determined up to 45 days after the infusion in one patient sampled over such a long period. Pharmacokinetics of JM-40 showed a linear behaviour. The final half-life of total Pt in plasma was 4.1 +/- 0.9 days. The disposition of JM-40 was similar to that of ultrafilterable Pt in respect to t1/2 alpha (10 and 13 min), t1/2 beta (44 and 57 min), volumes of distribution Vc (11 and 121) and Vss (17 and 201), systemic clearance (256 and 223 ml min-1), renal clearance (69 and 73 ml min-1) and metabolic clearance (183 and 154 ml min-1). During the first 6 h 27 +/- 9% of the administered dose was excreted as JM-40. Cumulative platinum excretion in the urine amounted to 29 +/- 13% and 60 +/- 13% over the first 6 h, 24 h and 5 days, respectively. The uptake of platinum in red blood cells was limited, comprising only 0.24 +/- 0.12% of the administered dose. Although JM-40 and carboplatin are structurally closely related, pharmocokinetics and toxicity of JM-40 were more similar to cis-platin than to carboplatin. 相似文献
92.
Perceptual asymmetry on a series of four specially constructed dichotic word tests was found to change as a function of the emotional quality of the words in the tests (P = 0.05). This was most pronounced in the case of positively valued words which produced an increase in asymmetry consistent with facilitated left-hemisphere function (P less than 0.004). Changes in asymmetry with emotion differed as a function of personality characteristics of the subjects, with repressors and high anxious subjects showing an increase with emotion while true low anxious subjects showed a decrease (P less than 0.02). Personality groups also differed in asymmetry on an emotionally neutral test (P less than 0.04) and in changes in asymmetry over time independent of emotion (P less than 0.001). These data suggest that emotion mediated activation of the left hemisphere may facilitate information processing within that hemisphere. Moreover, they indicate that dichotic listening tests may provide a non-invasive and inexpensive method for assessing emotion mediated changes in brain state that are clinically relevant. 相似文献
93.
94.
S B Wieslander B T Mortensen L Binderup N I Nissen 《European journal of haematology》1987,39(1):35-38
10 patients with CLL and 2 with CML were treated with gradually increasing doses of 1 alpha(OH)D3, up to 4 micrograms daily during 6 wk. 3 patients with preleukemia and 1 with myelofibrosis were treated with 2 micrograms daily of 1 alpha(OH)D3 for a prolonged period up to 17 wk. The treatment with 1 alpha (OH)D3 did not result in changes of disease parameters in any of the patients under study. Receptor studies for 1,25(OH)2D3 were performed in 8 CLL patients and revealed only 1 patient with increased specific receptor binding capacity. The maximum tolerable dose of 1 alpha(OH)D3 varied individually, but was in the range of 2-4 micrograms daily. 相似文献
95.
96.
97.
Carnitine status in Reye and Reye-like syndromes 总被引:4,自引:0,他引:4
Fourteen children with the following Reye and Reye-like syndromes were studied to determine each patient's carnitine status: valproate-induced Reye-like attack, ornithine transcarbamylase deficiency, systemic carnitine deficiency, methylmalonic acidemia, and propionic acidemia. Reduced free carnitine and increased serum and urine acylcarnitine levels were found in all patients except for 2 with Reye syndrome, in whom serum creatinine levels were mildly elevated and serum free carnitine levels were not reduced. The renal free carnitine reabsorption rate was reduced in all cases. The free carnitine content of autopsied liver samples were reduced in 2 Reye syndrome patients, 2 OTC deficiency patients, and in a single systemic carnitine deficiency patient. The observed secondary free carnitine deficiency may be a factor in the pathogenesis of Reye and Reye-like syndromes. 相似文献
98.
Alpha-adrenoreceptor reagents. 4. Resolution of some potent selective prejunctional alpha 2-adrenoreceptor antagonists 总被引:1,自引:0,他引:1
A P Welbourn C B Chapleo A C Lane P L Myers A G Roach C F Smith M R Stillings I F Tulloch 《Journal of medicinal chemistry》1986,29(10):2000-2003
The resolution of three 2-substituted derivatives of idazoxan is described. The enantiomers show large separations in activity in a variety of in vitro and in vivo tests, and the active isomers are all potent and selective antagonists at the alpha 2-adrenoreceptor. The significance of these results in relation to those published on the enantiomers of idazoxan and to those on optically active alpha 2-adrenoreceptor agonists is discussed. 相似文献
99.
Tauseef Ahmed Alan Yagoda Howard I. Scher Cora Sternberg Robin C. Watson 《Investigational new drugs》1986,4(2):171-174
Summary Deaza-aminopterin is a folate analog which is transported more rapidly than methotrexate into cells and appears to be more active than methotrexate against human and animal tumor in vitro. Fifteen patients with advanced urothelial tract cancer were given deaza-aminopterin 30–37.5 mg/m2 IV QW. In responding patients drug was given QOW after 4–6 consecutive doses. Doses were escalated or de-escalated by 7.5 mg/m2 depending on toxicity. Twelve patients had received prior chemotherapy which included methotrexate in nine. Three patients achieved a partial remission lasting 1, 3, and 3 months respectively: all responders had previously failed methotrexate after an initial response to a methotrexate containing regimen. None of the six patients who were methotrexate naive responded to deaza-aminopterin; 3 subsequently received methotrexate without response. Mild mucositis was universal and in 5 was severe. Six patients had an increase in liver transaminases probably secondary to anti-folate hepatotoxicity. Other toxicities included diarrhea, nausea, skin rash and fever. Further studies are needed to define the precise efficacy of deaza-aminopterin in patients with urothelial tract cancers. 相似文献
100.