The detection of chemical impurities by high pressure liquid chromatography and the genetic activity of medical grades of pyrvinium pamoate inSaccharomyces cerevisiae andSalmonella typhimurium

The genetic activity of several medical grades of the anthelmintic drug pyrvinium pamoate, which is a dipyrvinium salt, was studied in a diploid mitotic recombination and gene conversion assay (strain D5 ofSaccharomyces cerevisiae), and in several haploid yeast reversion assays (strains XV185-14C, XY718-1A, and 7854-1A). All of the samples were recombinogenic in strain D5 and mutagenic in the haploid strains, however, the degree of genetic activity varied considerably among the medical grades of pyrvinium pamoate that were tested. Similarly, these samples varied in degree of mutagenicity when they were tested in strains TA97, TA98, TA100, and TA102 ofSalmonella typhimurium, but some of the medical grades of pyrvinium pamoate were mutagenic both in the presence and in the absence of the metabolic transformation system, whereas other medical grades of the drug required such activation to be mutagenic. In addition, the medical grades and dosage forms of several brands of pyrvinium pamoate were examined for purity by fluorescence high pressure liquid chromatography (HPLC) using a methanol:water (9010) solvent system. The HPLC data indicate that monopyrvinium salts are the major contaminants in these pharmaceuticals. In general, there is a correlation between the degree of genetic activity and toxicity, and the number and relative quantity of impurities found in each sample.     

HPLC测定复方阿苯达唑片的含量

目的　用HPLC法测定复方阿苯达唑片中阿苯达唑和双羟萘酸噻嘧啶的含量。方法　采用硅胶柱 ,以乙腈 -混合液[水 -乙酸 -二乙胺 (2 .5∶2 .5∶1) ](5 4∶1)为流动相 ,检测波长 2 88nm。结果　阿苯达唑的线性范围为 0 2～ 0 6 μg ,回归方程为 :Y =1.832× 10 6X +7.2 84× 10 3 (r=0 .9998) ;双羟萘酸噻嘧啶的线性范围为 0 .8～ 2 .4 μg ,回归方程为 :Y =1 2 5 5× 10 6X -1 736× 10 4(r=0 .9995 )。结论　所用方法简便、快速 ,准确、可靠。     

复方阿苯达唑驱除肠道线虫的现场观察

目的：观察复方阿苯达唑（每片含阿苯达唑６７ｍｇ和噻嘧啶８３．３ｍｇ基质）的驱虫效果。方法：对成人钩虫感染者１８６４例、蛔虫感染者１５６８例和鞭虫感染者１７８５例及儿童蛲虫感染者３７３例，随机分组，比较服用单剂复方阿苯达唑３片或２片与单剂阿苯达唑４００ｍｇ或噻嘧啶３０ｍｇ（含基质１０ｍｇ）／ｋｇ的驱虫效果和副作用。结果：成人复方阿苯达唑３片和２片的虫卵阴转率，钩虫分别为６５．０％和５２．７％（Ｐ＜０．０１），蛔虫均为１００％，鞭虫分别为２６．５％和１９．２％（Ｐ＜０．０１）。３片的驱钩虫效果显著优于阿苯达唑和噻嘧啶组（Ｐ均＜０．０１）。２片的驱钩虫效果亦优于噻嘧啶（Ｐ＜０．０１），与阿苯达唑无显著性差异，但驱鞭虫效果低于阿苯达唑。２－６岁儿童服复方阿苯达唑１．５片的，蛲虫卵阴转率为１００％，显著优于噻嘧啶（Ｐ＜０．０１）。复方阿苯达唑的驱虫作用快速，副作用轻，对血象、肝肾功能和心电图无显著影响。结论：复方阿苯达唑具有阿苯达唑和噻嘧啶两药的协同作用。     

复方制剂中双羟萘酸噻嘧啶及阿苯达唑含量测定方法的研究

本文采用双波长法分别测定驱虫药复方制剂的有效成份双羟萘酸噻嘧啶及阿苯达唑，进行了方法学研究、线相关系、加样回收等实验工作，两种效成分的回收率分别为１００．６±０．６８％，９９．２７±０．５９％（ｎ＝２），含量在其标示量的±２０％范围内线性关系良好，分别为ｒ＝０．９９９９，ｒ＝－９９９８。     

CSF Monoamine Metabolism in Patients with Tardive Dyskinesia: Effect of Oxypertine and Hydroxyzine Pamoate

Abstract: Cerebrospinal fluid (CSF) HVA, MHPG, 5-HIAA, cAMP and cGMP concentrations were measured in schizophrenic patients with tardive dyskinesia before and after a three-week administration of oxypertine (n = 4), hydroxyzine pamoate (n = 4) or placebo (n = 4). The oxypertine administration resulted in a reduction of the CSF HVA concentration and an elevation of the MHPG and cAMP concentrations, associated with a clinical improvement in tardive dyskinesia. The hydroxyzine administration reduced the CSF 5-HIAA concentration in all the patients and the CSF HVA concentration in two of four patients with a clinical improvement. A reduction in the CSF HVA concentration associated with possible therapeutic effects of oxypertine or hydroxyzine may suggest the normalization of a hyperdopaminergic state. Discussions were held that functional disorders of not only the dopaminergic system but the norepinephrinergic and serotoninergic systems may relate to the pathogenesis of tardive dyskinesia.     

Schistosomiasis and soil-transmitted helminthiasis: common drugs for treatment and control

Schistosomiasis is a disease caused by parasitic trematode worms (schistosomes) that currently affects 200 million people living in tropical and subtropical environments. It is a chronic disease and the latest estimates for sub-Saharan Africa are that it kills > 200,000 people every year. Soil-transmitted helminthiasis (STH) is caused by intestinal nematodes. More than 2 billion people are infected worldwide and the disease burden might approach that of malaria. Recognising the enormous public health significance of schistosomiasis and STH, particularly among the poor, and in view of readily available drugs that are safe, efficacious and inexpensive, the World Health Assembly recently set forth a resolution for a combined approach for morbidity control of both diseases. This review briefly summarises the geographical distribution, life cycle and global burden of schistosomiasis and STH. The current arsenal of drugs available for morbidity control, including discovery, chemistry, pharmacological properties and aspects of therapeutic efficacy and adverse events in clinical human use is then discussed. The emphasis is on praziquantel, oxamniquine and artemisinin derivatives (against schistosomes) and albendazole, mebendazole, levamisole, pyrantel pamoate and other compounds (against intestinal nematodes). The experience gained with combination chemotherapy in schistosomiasis and STH is briefly discussed. Finally, current research needs and the critical importance for development of novel anthelmintic drugs, so that chemotherapy can continue to serve as the backbone of integrated and sustainable control of schistosomiasis and STH, is highlighted.     

Pyrvinium pamoate inhibits proliferation of myeloma/erythroleukemia cells by suppressing mitochondrial respiratory complex I and STAT3

Pyrvinium pamoate (PP), a classical anthelminthic, potently inhibited proliferation and STAT3 Tyr705 phosphorylation of human myeloma (U266B1 and PCM6)/erythroleukemia (HEL 92.1.7) cells. PCM6 cell proliferation was markedly impaired by STAT3 siRNA knockdown. PP inhibited ATP production/O(2) consumption in those three cells and mitochondrial respiratory complex (I+III, but not II+III) activity in mouse kidney mitochondrial fractions. PP inhibition of ATP production, STAT3 Tyr705 phosphorylation, and proliferation was absent in mitochondrial DNA-deficient HEL 92.1.7-ρ(0) cells. Moreover, PP acted synergistically with dexamethasone to inhibit PCM6 cell proliferation. In conclusion, we identified PP as a potential anticancer drug directed against mitochondrial respiratory complex I/STAT3.     

Étude coût-efficacité du pamoate d’olanzapine : analyse en miroir sur un an

IntroductionOlanzapine pamoate has a higher cost of treatment than the oral form and requires administration in a hospital setting (unlike other long-acting antipsychotics), and the cost-effectiveness of this treatment may be questioned. Many scientific societies and national health systems are increasingly interested in the pharmacoeconomic impact of health products. The search for efficacy of a treatment can be done in two ways: medico-economic modeling studies or observational studies i.e. randomized controlled trials or mirror studies. The models are based on theoretical models from published clinical data simulating the course and evolution of patient health conditions, which benefit from a particular therapeutic strategy. Even if the design of observational mirror studies makes it possible to get closer to the clinical reality by observing the patient before and after the initiation of the treatment, the majority of the pharmacoeconomic studies published on olanzapine pamoate are modeling works that do not reflect actual conditions of care. The Guillaume Régnier Hospital Center in Rennes has a large cohort of patients treated with olanzapine pamoate: 121 instauration treatments are recorded from April 1, 2010 to Mars 1, 2015. The objective of this study is to evaluate the cost-effectiveness of olanzapine pamoate in actual clinical practice.MethodsThis is a one-year cost-effectiveness retrospective observational mirror-image study of a cohort of 52 patients with schizophrenia who were treated for at least three months with olanzapine pamoate. The primary efficacy endpoint is the differential in the number of full-time hospitalizations before and after the introduction of olanzapine pamoate versus the hospital cost differential. The secondary criteria are the difference of the number of the days spent in hospital and the number of outpatient consultations between the year preceding the injection and the year following it. The results were calculated on the general cohort and within 2 subgroups: patients treated for more than one year and those receiving less than one year of treatment with olanzapine pamoate.ResultsFifty-two patients were included (median age = 35 years, sex ratio H/F = 2.7) and only 38.5% discontinued treatment. For patients who maintained long-acting treatment, they received a dosage of 25 mg oral olanzapine (min = 7.5 mg, max = 60 mg), 5 mg more medially than the group having stopped the olanzapine pamoate (20 mg; min = 10 mg, max = 40 mg). The majority of these patients were receiving off-label authorized marketing doses of oral olanzapine, whereas 22% of them had off-label dosages of olanzapine pamoate. The main causes of discontinuation were symptom persistence, loss of vision and the occurrence of adverse effects (including weight gain and sedation). Olanzapine pamoate significantly reduced the number of hospitalizations compared to the previous management strategy (1 less hospitalization, P < 0.001 in patients treated more than one year and in the general cohort). As a logical consequence the number of hospitalization days in day care increased after the establishment of this long-acting antipsychotic with hospital reserve status (18 in median; min = 0, max = 159). We observed a non-statistically significant tendency of decrease in the number of days of full-time hospitalization and an increase in the number of ambulatory procedures, particularly in patients who have maintained the treatment for one year. This efficiency had a non-significant additional cost of €3361 per year. There was an average multiplication by 8,5 of the drug cost a year later in the general cohort (5.5 in the group of patients treated less than one year and 10.4 in the group of patients who maintained it a year). There was a 23,2% average increase in the cost of hospitalization in the general cohort (3.75 % in patients who maintained treatment compared to 48.9% in patients who discontinued treatment).ConclusionBy its mirror design, the study was placed in real conditions of care of the patient with schizophrenia. A total of 61.5% of patients maintained treatment with olanzapine pamoate for a minimum of one year. This APAP is more effective without significantly increasing the cost compared to the previous therapeutic strategy (including oral olanzapine). The additional cost is partly due to the administration restriction in a hospital setting in relation to risk of Post-Injection Delirium/Sedation Syndrom (PDSS). There is currently no acceptable efficiency limit. The results of this cost-effectiveness analysis cannot be extrapolated to the other long-acting antipsychotics since it is the only one with hospital reserve status. The current limitations of medico-economics in psychiatry derive from the heterogeneity of clinical forms and the management of mental pathologies.     

浙江省嵊县散居儿童和纺织厂幼儿园儿童蛲虫感染和治疗效果观察

作者报道浙江省嵊县两个村学龄前散居儿童和纺织厂幼儿园儿童蛲虫感染情况;用透明胶纸玻片肛检法,发现虫卵者为阳性,并给予治疗。检查散居儿童100人,幼儿园儿童80人,感染率分别为64％、68.8％,经统计分析两者无显著性差别。散居和集体儿童的不同年龄组之间感染率有显著差别,5～8岁儿童感染率明显高于1～4岁儿童。将72例蛲虫病患儿随机分为两组,用噻嘧啶治疗,结果以每天7.5mg/kg顿服,连服2d的疗法更为可取。