高效液相色谱法测定人血浆中阿莫西林浓度及药代动力学

高效液相色谱法测定人血浆中阿莫西林浓度及药代动力学谭力周继红罗楠袁倚盛（南京军区南京总医院中心仪器分析科，南京２１０００１）阿莫西林（ａｍｏｘｉｃｉｌｉｎ）为β内酰胺类抗生素，其抗菌谱广，口服受食物影响小，对大多数病人耐受性良好，因而在临床上得以广泛...     

Critical illness polyneuromyopathy after artificial respiration.

Up to now, 71 critically ill patients have been reported with neuromuscular complications after artificial respiration. The authors review the literature and present data of a personal series of 22 patients all suffering from severe flaccid tetraparesis and muscle atrophy, which developed after an average of two weeks artificial respiration. The prognosis was relatively good in those surviving the primary disease. The multiconditional causes are discussed with emphasis on the combination of polyneuropathy and myopathy. Tumor necrosis factor (TNF), a key mediator of sepsis, which also has an influence on muscle and nerves, is mentioned as a possible cause of this illness.     

Relationship between mephenytoin oxidation polymorphism and phenytoin, methylphenytoin and phenobarbitone hydroxylation assessed in a phenotyped panel of healthy subjects.

1. In a phenotyped panel of healthy subjects correlations were studied between the oxidation of mephenytoin, phenytoin, methylphenytoin and phenobarbitone, with respect to the formation of their 4-hydroxy metabolites (OH-). 2. On different occasions phenotyped extensive metabolizers (EM; n = 16) and poor metabolizers (PM; n = 4) of mephenytoin received phenytoin (100 mg), methylphenytoin (100 mg) and phenobarbitone (50 mg) and urine was collected up to 24 h. The excreted 4-hydroxy metabolites of all compounds were measured by h.p.l.c. 3. Urinary recovery of OH-phenytoin was 31.0 +/- 11.7%, of OH-methylphenytoin 3.4 +/- 2.7% and of OH-phenobarbitone 1.4 +/- 1.2%. No correlation was found between the recovery of OH-mephenytoin and OH-phenytoin. A subject who produced virtually no OH-phenytoin was an EM of mephenytoin, confirming a dissociation of mephenytoin polymorphism and phenytoin hydroxylation. 4. The correlation coefficient for OH-mephenytoin and OH-methylphenytoin recovery was 0.71 (Spearman rank, P = 0.002). The PMs of mephenytoin excreted the least amount of OH-methylphenytoin, suggesting a cosegregation of the 4-hydroxylation pathways. No correlation was found between the urinary recovery of OH-phenobarbitone and that of the other 4-hydroxy metabolites.     

抗胆碱药3-(2-苯基-2-环戊基-2-羟基-乙氧基)奎宁环烷的立体化学和构效关系

研究了强效抗胆碱药dl-3-(2-苯基-2-环戊基-2-羟基-乙氧基)-奎宁环烷的四个光学异构体的两种不对称合成方法,用HPLC检测了异构体含量,讨论了构效关系。     

Topoisomerase I inhibitors: the relevance of prolonged exposure for present clinical development.

Topoisomerase I inhibitors constitute a new class of anti-cancer agents. Recently, topotecan and irinotecan were registered for clinical use in ovarian cancer and colorectal cancer respectively. Cytotoxicity of topoisomerase I inhibitors is S-phase specific, and in vitro and in vivo studies have suggested that, for efficacy, prolonged exposure might be more important than short-term exposure to high concentration. Clinical development of those topoisomerase I inhibitors that have reached this stage is also focused on schedules aiming to achieve prolonged exposure. In this review, we summarize all published preclinical studies on this topic for topoisomerase I inhibitors in clinical development, namely 20-S-camptothecin, 9-nitro-camptothecin, 9-amino-camptothecin, topotecan, irinotecan and GI147211. In addition, preliminary data on clinical studies concerning this topic are also reviewed. The data suggest that prolonged exposure may indeed be relevant for anti-tumour activity. However, the optimal schedule is yet to be determined. Finally, clinical data are yet too immature to draw definitive conclusions.