Kalman滤波分光光度法同时测定多相脂质体口服液中氟尿嘧啶和尼泊金的含量

本文提出了对测量值平滑后,用Kalman滤波分光光度法同时测定多相脂质体口服液中氟尿嘧啶和尼泊金的含量,改善了滤波效果,较好地解决了复杂基质存在下多组分的同时测定。用人工合成样考察表明,在269～273nm间滤波结果较好。用分别相当制剂标示量80,100,120%的两组分九种可能组合人工合成样品考查结果表明,氟尿嘧啶和尼泊金的回收率分别为99.3～102.6%和97.8～103.0%;当存在系统误差时,回收率分别为99.4～102.7%和97.0～102.9%     

Activation-dependent alpha5beta1 integrin-mediated adhesion to fibronectin decreases proliferation of chronic myelogenous leukemia progenitors and K562 cells

Chronic myelogenous leukemia (CML) is a malignant disease of the hematopoietic stem cell characterized by abnormal circulation and proliferation of malignant progenitors. In contrast to their normal counterparts, CML progenitors adhere poorly to bone marrow stroma or fibronectin (FN). Aside from anchoring progenitors in the marrow microenvironment, beta1 integrin-dependent adhesion of normal progenitors is also associated with inhibition of their proliferation. As the beta1 integrin expression on CML progenitors is normal, we hypothesized that decreased integrin affinity may underlie the abnormal adhesive and proliferative characteristics of CML progenitors. We examined the effect of affinity modulation by the activating antibody 8A2 on the adhesion and proliferation of CML progenitors and the CML cell line, K562. 8A2 induced alpha5Beta1-dependent adhesion of Philadelphia chromosome-positive (Ph+) CD34+/HLA-DR+ cells and K562 cells to FN. Increased adhesion was 8A2- and FN concentration- dependent, time-dependent, and energy-dependent. Further, 8A2-induced adhesion to FN significantly inhibited the proliferation of malignant CML progenitors as well as K562 cells independent of cell differentiation, necrosis, or apoptosis. These studies demonstrate that affinity modulation of the alpha5Beta1 integrin on CML progenitors and K562 cells by 8A2 results in increased adhesion to FN with subsequent decreased proliferation, suggesting that decreased beta1 integrin affinity contributes to the abnormal circulation and proliferation of malignant progenitors in CML.     

Effect of ponsinomycin on the pharmacokinetics of dihydroergotamine administered orally

Ponsinomycin is a new macrolide antibiotic. Its effect on DHE pharmacokinetics was investigated in this study. Twelve young healthy volunteers received a single 9 mg oral dose of DHE before and on the 8th day of treatment (800 mg twice daily) with ponsinomycin. DHE was assayed in plasma by RIA. Because of low plasma levels, only peak concentrations could be accurately compared for a ponsinomycin effect. We observed a 3-40-fold increase in maximum DHE plasma levels in the majority of cases and a much more important effect on one occasion, when DHE was administered in the presence of ponsinomycin. These data are consistent with an increase of DHE bioavailability in the presence of ponsinomycin, probably related to a reduction of its first-pass elimination. This pharmacokinetic interaction is likely to have clinical consequences and administration of ponsinomycin should be avoided in patients treated orally with DHE.     

Pharmacokinetic characterization of mitonafide in man.

The pharmacokinetic behavior of mitonafide after intravenous administration (1 h infusions) to patients (118-180 mg/m2) can be described by an open three compartment body model. Mitonafide distributes quasi-instantaneously in a central distribution volume of 102 l/m2 (median) from which it equilibrates with two peripheral compartments of 106 and 258 l/m2, respectively. Its disappearance from plasma is triexponential with half-lives of 0.28, 2.0 and 26.9 h, resulting in a clearance of 69 l/h/m2. This clearance is mainly due to the biotransformation of mitonafide leading among others to amonafide, N-acetyl-amonafide, and N-desmethyl-amonafide, which build up substantial concentrations in plasma. Their quantitative importance in terms of exposures (AUC) relative to the parent compound are 86, 197 and 28%, respectively. Terminal elimination from plasma proceeds with half-lives of 34.3, 17.6 and 27.5 h.     

吸收度线性组合法测定乳糖干扰下扑尔敏含量

本文通过乳糖干扰下扑尔敏的含量测定,主要探讨及考察了非专属的一般操作误差对方法的正确评价和比较的影响,提出了检查一般操作误差大小的方法,进一步确认了吸收度线性组合法的优越性。同时讨论了吸收度线性组合法的组合精度与组合点数之间的关系,以及主组分吸收度过小对测定精度的影响,考察了吸收度比值在确定组合方式中的重要性。     

安乃近代谢物4-甲氨基安替比林的HPLC测定及其鼻腔滴剂在人体的相对生物利用度

安乃近进入血液后,迅速、完全地被代谢为4-甲氨基安替比林(MAA),血浆中检测不出安乃近原型药,故血浆MAA水平可反映安乃近的吸收情况。本文建立了MAA的HPLC测定法,并用于安乃近鼻腔滴剂人体内药代动力学和肌内注射剂及口服片剂的相对生物利用度研究。结果表明鼻腔滴剂较口服片剂吸收快,较肌内注射剂生物利用度高。     

Failure in the rate adaptation of the atrial refractory period: its relationship to vulnerability

We evaluated the relationship of rate-dependent changes in atrial refractoriness to atrial vulnerability in 39 patients. Vulnerability was considered present when sustained atrial tachyarrhythmias, lasting longer than 1 minute, could be provoked with one to three extra stimuli. Adaptation of atrial refractory period duration to rate was defined as: normal: steep rate reduction with a linear correlation slope value of 0.08 or more; non-adaptation: absence of rate reduction, the slope value being 0 to 0.01; poor adaptation: slight reduction with rate, the slope having values of 0.02 to 0.07. Increased vulnerability was demonstrable in 16 of 17 patients with non-adaptation of the effective refractory period (ERP), and in 10 of 10 with a similar defect of the functional refractory period (FRP); in the intermediate category (poor adaptation) the results for ERP and FRP were 7/11 and 5/6. By way of contrast when both measurements showed normal adaptation, vulnerability was elicited in 2/9 patients. The significance between these groups showed P less than 0.005. Of 17 patients with atrial arrhythmia by Holter, 14 showed poor or non-adaptation of the ERP. It is suggested that poor or absent rate adaptation of the atrial refractory period, and a propensity to atrial fibrillation or flutter, constitute a clinical entity not previously described.