Clinical use of immunosuppressive drugs: part II.

In haematological diseases, insufficient data has been accumulated to evaluate the efficacy of immunosuppressive drug treatment in patients with erythroid aplasia or sideroblastic anaemia. Cyclophosphamide may be efficacious in inhibiting circulating anticoagulants in patients who need continued replacement of clotting factors. Azathioprine, 6-mercaptopurine, cyclophosphamide and vincristine have been used successfully in treating patients with idiopathic thrombocytopenic purpura, and some patients with auto-immune haemolytic anaemia may benefit from the addition of purine analogues. However, the use of immunosuppressive therapy seems to accelerate the presence of haematological malignancies in patients with macroglobulinaemia. In gastro-intestinal diseases, uncontrolled studies have shown nitrogen mustard, 6-mercaptopurine and azathioprine to be of modest benefit to patients with ulcerative colitis and Crohn's disease. In a controlled trial azathioprine plus prednisone proved more effective than prednisone alone in sustaining remission in patients with Crohn's disease. In patients with either chronic active hepatitis or primary biliary cirrhosis, however, there seems to be no benefit from immunosuppressive therapy for primary treatment of these diseases. Cyclophosphamide, azathioprine and methotrexate have all been used with some success in treating patient with uveitis, and in a controlled trial cytarabine has been shown to be beneficial to patients with herpes ophthalmicus. However, no benefit has been shown to patients with the eye changes of Graves' disease with either azathioprine or methotrexate. Patients with Paget's disease appear to be helped by mithramycin. Cyclophosphamide, chlorambucil and azathioprine are ineffective in treating patients with multiple sclerosis. 6-Mercaptopurine, azathioprine, methotrexate and cyclophosphamide have all produced some benefit in patients with myasthenia gravis, and some patients with idiopathic pulmonary haemosiderosis have responded to azathioprine, 6-mercaptopurine and cyclophosphamide. Alkylating agents have proved useful in treating some patients with asthma and in treating frequent relapsers among children with the nephrotic syndrome. In adults with membrano-proliferative glomerulonephritis some patients have responded to combination therapy with cyclophosphamide, azathioprine and corticosteroids. Immunosuppressive therapy is also indicated in prolonging graft survivals in patients receiving organ transplants. Drug toxicities of immunosuppressive agents are discussed. Their long-term effects, including mutagenic potential, have as yet not been fully elucidated.     

UV spectrophotometry in drug control. 31. Spectrophotometric behavior of drugs with dibenzo-p-thiazine chromophores

The results of a systematic examination of the spectra of 34 drugs with dibenzo-p-thiazine chromophores in the ultraviolet and visible range were evaluated. The substances under study were subdivided into 10 different types corresponding to a different substitution in position 3 and in one case in position 5 of the phenothiazine ring system. All of these types are characterized by the bands E, K and B which are--with only a few exceptions--separated by well developed absorption minima.     

Gas-liquid chromatography with Fourier-transform infrared spectrophotometry. Application in the analysis of drugs. 2: Benzodiazepines]

High working temperatures were used during the separation of benzodiazepines by capillary gas chromatography with Fourier transform infrared detection (FTIR). Spectral identification of these drugs give very good results with 10 micrograms of drug injected. On the contrary, the precision of the quantitative determination is poor.     

New drugs for osteoporosis. Comparison of the costs and required returns with those of other drugs intended for long-term use.

Specific regulatory guidelines dictate that developing a new drug for osteoporosis will be significantly more expensive and take at least 2 years longer in comparison with other long-term therapies developed using the International Committee on Harmonisation (ICH) general guidelines. Assuming similar attrition rates, the minimal additional uncapitalised cost is $US86 million for nonestrogen osteoporosis compounds following a minimum programme designed to gain indications for both treatment and prevention. The excess expenditure is created by the size requirements for phase III fracture trials in both the European Union (EU)/US and Japan. The after-tax cash flows to the point of launch discounted at 11% are $US102 million greater, reflecting the additional effect of delayed time to market. Assuming similar lifecycles, the peak sales required to return the investment on an osteoporosis drug will be a minimum of $US95 million greater per launched compound. Many ongoing osteoporosis programmes are substantially larger than the theoretical minimum. The costs of substantially increasing the sample size in phase III trials mean that blockbuster revenues will be required to break even. However, the potential cost of a delayed launch because of fracture efficacy being incompletely proved is so substantial that fracture trials need to be powered conservatively to decrease the chances of this eventuality.     

双波长法考察注射用草酸铂的稳定性

目的:考察不同温度下注射用草酸铂(L-OHP)在5%葡萄糖注射液(5%GS)中及与地塞米松磷酸钠注射液配伍的稳定情况.方法:采用双波长分光光度法测定各溶液中L-OHP的含量,同时测定各溶液的pH、观察外观性状及紫外光谱的变化情况.结果:L-OHP 5%GS及L-OHP 5%GS 地塞米松磷酸钠注射液自然光下、温度20℃或35℃,12h内各种溶液的外观无明显变化,pH值无明显变化.但L-OHP的含量受温度和配伍药物的影响较大:单药20℃,6h含量为初始浓度的95%以上,8h为94%;35℃6h含量约为初始浓度的94%,8h约为93%;与地塞米松磷酸钠注射液配伍:20℃1h时L-OHP含量约为初始浓度的91%.结论:临床应用L-OHP时宜现用现配.L-OHP不宜与地塞米松磷酸钠注射液伍用.