The consequences of H2 receptor antagonist — piroxicam coadministration in patients with joint disorders

Summary A randomised crossover study was performed in subjects with rheumatoid arthritis (or other arthropathies) to investigate if any alteration in the steady pharmacokinetics of the NSAID piroxicam (a drug which is extensively metabolised via cytochrome P450) or its major metabolites occurred as a result of coadministering either cimetidine or nizatidine.Twelve females and 2 males with mean age, weight, and albumin concentrations of 58 years, 61 kg, and 40 g·L^–1 respectively, completed the study. Comparisons were made between the following parameters: plasma piroxicam AUCs [AUC_0-24(P)], plasma 5-hydroxypiroxicam AUCs [AUC_0-24(5-OHP)], the ratio of these i.e. AUC_0-24(5-OHP):AUC_0-24(p), the % piroxicam daily dose excreted in urine as 5-hydroxypiroxicam (before and after glucuronidase incubation); and the mean of the steady state trough piroxicam, and 5-hydroxypiroxicam concentrations (obtained during each study phase in addition to the wash-out period).A statistically significant difference as a result of initiating either cimetidine or nizatidine was obtained only for the ratio AUC_0-23(5-OHP):AUC_0-24(P). This was indicative of a weak potential to inhibit piroxicam hydroxylation.No clinically significant alteration in the steady state pharmacokinetics of piroxicam occurred in these subjects as a result of cimetidine or nizatidine coadministration. Consequently it is unlikely that any adverse events would arise from these combinations.     

Preclinical Drug Metabolism in the Age of High-Throughput Screening: An Industrial Perspective

With the advent of genomics, combinatorial paradigms and high-throughput screen (HTS)-based pharmacological testing, the number of compounds flowing through the discovery pipeline is likely to escalate. At the same time, with increased knowledge of the human drug-metabolizing enzymes and the availability of in vitro absorption-metabolism (AM) models, Preclinical Drug Metabolism is poised to meet the challenges of HTS. In order to be successful, however, a rational HTS strategy (vs. serendipitous HTS) has to be employed. Such a strategy is based on automation, validation and integration of in vitroAM models and database management (AVID). A generalized strategy for rational (AVID-based) HTS in Preclinical Drug Metabolism is described briefly.     

Circular dichroism detection in high-performance liquid chromatography: Evaluation of the anisotropy factor

The application of a circular dichroism (c.d.) detection system in HPLC using a chiral stationary phase is presented. The simultaneous measurement of the absorbance and c.d. signal allows the evaluation of the anisotropy factor (g = Δ/) and thus the determination of the enantiomeric excess (e.e.) of the eluates. When this detection system is used in preparative chiral chromatography the collection of the enantiomeric fractions can be readily optimized.     

地塞米松促胎儿肺成熟的三种用药方式对母体糖代谢的影响

【目的】探讨地塞米松的用药方式对孕妇糖代谢的影响。【方法】对 1999年 9月至 2 0 0 1年 1月在本院住院的15 0名不同用药方式使用地塞米松促胎儿肺成熟的孕妇进行研究 ,在用药前及用药后 18～ 2 4h抽取肘前静脉血查空腹血糖、血浆C肽 ,糖负荷后 2h血糖、血浆C肽。【结果】使用地塞米松后 ,空腹血糖值、糖负荷后 2h血糖值、空腹C肽及糖负荷后 2hC肽值较用药前高 ;用药方式对母体空腹血糖值和空腹C肽值的影响差异无统计学意义 (P >0 0 5 ) ,对母体糖负荷后 2h血糖值和糖负荷后 2hC肽值的影响差异有统计学意义 (P <0 0 5 ) ;不同糖代谢状态的受试者使用地塞米松后 ,空腹C肽值、糖负荷后 2hC肽值的改变差异有统计学意义 (P <0 0 5 )。【结论】孕妇使用地塞米松促胎儿肺成熟对母体的糖代谢均有一定程度的影响 ,用药过程中和用药后需严密监测母体血糖和胎儿宫内状况     

放射性碘标记的抗肺癌单克隆抗体在载瘤裸鼠体内的代谢

放射性碘标记的抗人肺癌单克隆抗体2E3和6DI注入载人肺癌移植瘤裸鼠体内,静脉血放射性-时间曲线符合二室开放模型;血放射性清除半减期为3.4d,表观分布容积636ml/kg;标记抗体在体内的脱碘率为18.6％,脱落的放射性碘绝大部分从尿排出。腹腔给药吸收快,半吸收期2.08h,生物利用度89％。~(125)I标记的单克隆抗体注射后1～3d,放射性主要分布在肿瘤、血、肝、脾中,其次为肺、肾、胃、小肠;此后,血和正常组织的放射性下降,肿瘤中的放射性较高。~(131)I标记的单克隆抗体能使移植瘤清晰显像。     

异环磷酰胺为主的联合方案治疗晚期复发鼻咽癌

[目的]观察比较异环磷酰胺(IFO)、顺铂(DDP)、5-氟尿嘧啶(5-Fu)联合方案(IPF方案)与DDP,5-Fu(PF方案)治疗晚期复发鼻咽癌(Ⅲ-Ⅳ期)的近期疗效及毒副反应。[方法]136例均经病理证实为晚期复发鼻咽癌患者,随机分为IPF组69例,PF组67例(对照组)[结果]IPF组和PF组有效率分别为69.56％(48/69)和43.3％(29/67),两组间差异有显著性(X2=8.519,P<0.01)。中位生存期:IPF组16个月(8-34个月),PF组为6.5个月(4-21个月),两组间差异有显著性(X2=22.36,P<0.05)。毒副作用主要为骨髓抑制,Ⅲ-Ⅳ度白细胞下降率IPF组为49.4％,PF组为5.97％,两组差异有显著性(X2=29.54,P<0.01)。Ⅲ-Ⅳ度血小板下降率IPF组为29.18％,PF组为0％(X2=30.29,P<0.01);Ⅲ-Ⅳ度消化道反应两组的发生率分别为15.94％和11.94％(x2=0.234,P>0.01).且以Ⅲ度为主。[结论]以IFO为主的方案联合治疗晚期复发鼻咽癌疗效好,毒副反应能耐受,可作为一线方案。     

奥兰扎平治疗精神分裂症58例临床观察

目的观察奥兰扎平治疗精神分裂症的临床疗效与安全性.方法选择58例精神分裂症病人,开始给予奥兰扎平5mg*d-1,3d后根据临床疗效、副反应情况酌情增加剂量,最大剂量不超过20mg*d-1,治疗8周.治疗前及治疗后每2周用PANSS、CGI、TESS量表评定1次.结果治疗后PANSS总分、各因子分较治疗前显著下降(P<0.01),副反应主要有抗胆碱症状、过度镇静、体重增加、一过性丙氨酸氨基转移酶升高.结论奥兰扎平是一种安全、有效、副作用较轻的抗精神病药.     

注射法和手术法治疗瘢痕疙瘩效果比较

①目的　比较注射法和手术法治疗瘢痕疙瘩的效果。②方法　将 32例病人分A ,B组 ,A组采用以注射为主的综合疗法 ,应用特制的高压瘢痕注射器向瘢痕组织内注射确炎舒松A混悬液 ,注射间期瘢痕外涂去疤霜 ,再用透明敷料安舒妥密封 ,以使药物充分发挥作用和避免玷污衣物。B组采用以手术为主的综合疗法。术前1～ 2周在瘢痕组织的周围及基底部注射确炎舒松A混悬液 1～ 2次 ,然后将瘢痕全层切除。术后第 3周 ,切口处皮内注射少量药物 ,并配合安舒妥继续减张并密封药物于切口处 ,以防止切口展宽和瘢痕增生。③结果　A组 84块瘢痕达到治愈、显效、无效标准者分别有 5 7,2 6 ,1块 ,治愈率为 6 8% ,总有效率为 98% ;B组 32块瘢痕达到治愈、显效、无效标准者分别为 12 ,14 ,6块 ,治愈率为 37% ,总有效率为 81% ,两组疗效比较差异有显著性 (uc =5 .0 3,P <0 .0 5 )。④结论　以注射为主的综合疗法有效率高 ,但美容效果差。以手术为主的综合疗法可缩小皮损面积 ,但复发率较高。因此 ,应根据具体情况选择合适的治疗方法。