Clinical efficacy

Transfusion-induced autoimmune disease has been a significant complication in the treatment of patients who require multiple platelet transfusions. Platelets and lymphocytes carry their own blood group system, ie, the human leukocyte antigen (HLA) system, and it can be difficult to find an HLA matched donor. A mismatched platelet transfusion does not induce immediate adverse reactions, but may cause the patient to become refractory to the HLA type of the transfused platelets. The next time platelets with an HLA type similar to that of the transfused platelets are transfused, they are rejected by the patient and thus have no clinical efficacy. Exposure to platelets originating from different donors is minimized by the use of apheresis platelets. One transfusable dose (unit) of apheresis platelets contains 3-5 x 10 platelets. An equal dose of platelets from whole blood donation requires platelets from six to eight units of whole blood. Furthermore, platelets can be donated every 10 days, versus 10 weeks for whole blood donations. 

Clinically Efficacy. It is evident from the mechanism of action of antihistamines and the etiology of allergic diseases that antihistamines in no sense achieve a cure of the patient s allergy. After the adrninistration of a therapeutic dose, a temporal blockade of the effects of histamine is obtained. Whereas classical antihistamines needed at least twice daily adrninistration, for most of the more recently introduced agents adrninistration once daily is sufficient. 

Nevertheless, although the nonsedating H antihistamines have substantially improved the acceptabiUty and clinical efficacy of this class of compounds, these do not provide complete rehef eye disease responds less well than nasal disease, of the rhinitis symptoms nasal congestion responds poorly, breakthrough symptoms occur at high poUen counts, and only some 70% of patients report excellent to good treatment responses. Considerable research therefore still continues in the H antihistamine field. New antihistamines are continually being introduced. 

The mechanism of action of nootropic agents has been proposed to be their abiUty to faciUtate information acquisition, consoHdation, and retrieval (36). No one particular effect has been observed with any consistency for these agents, thus whereas a considerable amount of diverse preclinical pharmacological behavioral data has been generated using these compounds, the significance of these results in predicting clinical efficacy has not been established (43,44). Reviews on the biochemical and behavioral effects of nootropics are available (45—47). 

Elevation of cycHc AMP levels is also known to inhibit the release of inflammatory and contractile mediators from mast cells (42). The good clinical efficacy of P2" goiAsts may be related to this action because some members of this class of dmgs inhibit mediator release at the same concentrations at which they relax smooth muscle (43). In contrast to their effectiveness against immediate bronchoconstriction, P2" gonists do not inhibit the late asthmatic... 

A monograph (1) covers the pioneering period of sulfa dmg development and describes over 5000 sulfanilamide derivatives, their preparation, properties, trade names, and biological testing. This review is remarkably complete through 1944. Several thousand additional derivatives have been made since, but no comparable coverage is available. A definitive account of medical appHcations up to 1960 has been pubHshed (2), and a review of experimental antibacterial aspects has been made (3). Chapters on general aspects of sulfonamides and sulfones have appeared (4,5). A review of the clinical efficacy of trimethoprim—sulfamethoxazole has been pubHshed (6). 

Trigclic Antidepressants. Imipramine (38) was introduced in the late 1950s as one of the first pharmacotherapies for depression. At that time, chlorproma2ine [50-53-3] was the first effective antipsychotic treatment to be discovered. Researchers looked for similar chemical stmctures and imipramine was found to be effective in the symptomatic treatment of depression. Over the years, other congeners, such as desipramine (39), amitriptyline (40), and dothiepin (41), were synthesized and shown to be clinically efficacious antidepressant dmgs (121). These substances, known under the general mbric of tricycHc antidepressants, share a basic chemical stmcture comprising... 

The second-generation antidepressants, particularly RIMAs and SSRJs, are much less toxic ia overdose than the older TCAs and irreversible MAO inhibitors. However, similar to first-generation antidepressants, the therapeutic effect only becomes manifest after several weeks. Up to one-third of depressed patients are nonresponders. Ideally, an antidepressant would combine a more rapid onset of action with greater clinical efficacy and a higher responder rate, as well as even better tolerability. 

A combination of amphotericin B, miconazole (16), and rifampin (17) was used to successfully cure one patient. In addition, tetracycline (7) and minocycline (18) have been recommended although their clinical efficacy have not been estabUshed. No proven therapeutic agents exist for treating A.catbamoeba infections, however, the phenothiazines, trifluoperazine [117-89-5] and chlorpromazine [50-53-3], show promise in vitro. 

Outdated Human Blood. If clinical efficacy and safety of hemoglobin solutions can be shown, the demand for product would soon outstrip the supply of outdated human blood. About 12 million units of blood (1 unit 480 mL) are used in the United States each year, and only about 500,000 outdate. The primary use of blood is in intraoperative and emergency settings. The quantity of blood available for use in production of blood substitutes depends on safety and efficient usage of blood products as well as on the demands on blood suppHes. 

Acetyl-P-methylcholine chloride [62-51-1/, commonly called methacholine chloride, is a parasympathornimetic bronchoconstrictor with clinical efficacy in bronchial asthma (45,46). 

Chemistry, pharmacology, and clinical efficacy of the Chinese nootropic agent huperzine A, alkaloid from Hupenia sermta with annulated 2-pyridone and l-amino-3-methyl-9-ethylidenebicyclo[3.3.l]nona-2,6-diene fragments 99ACR641. 

Drugs can only be effective if enough is present at the target site and they can be harmful if too much is present so as to produce toxic side effects. Any attempt to draw conclusions about the clinical efficacy of a drug in a clinical trial without knowledge of the concentration at the target site is premature. The science of pharmacokinetics basically... 

Polmar, S., Diaz-Gonzalez, F., Dougados, M., Ortiz, P., and del-Miguel, G. (2004). Limited clinical efficacy of a leukotriene B4 receptor (LTBQ antagonist in patients with active rheumatoid arthritis (RA). Arthritis Rheum. 50 S239. 

Biologicals. Figure 3 Fusion protein construction combination of the molecular component of interest with the constant region (Fc) of an antibody molecule, usually immunoglobulin (lg)G1 Fc, imparts the Fc function on to the molecularcomponentfortherapeutic use. The example given is ofCTLA4-lg, derivatives of which have shown clinical efficacy in the treatment of rheumatoid arthritis and transplant rejection. 

The first clinical trials were performed in the 1970 s using a sodium salt derivative with an open E-ting (Fig. 1). However, the clinical efficacy was limited and severe bladder toxicity led to the termination of the clinical trials. The poor efficacy of the camptothecin sodium salt in those clinical trials was probably due to the fact that the open E-ring form of camptothecin (carboxylate derivative) is inactive as a Topi inhibitor. Following the identification of Topi as a target of camptothecin, water-soluble derivatives were produced by the pharmaceutical industry. Two of these water-soluble derivatives have been approved by the FDA for cancer treatment in the early 2000s topotecan and irinotecan. 

Mannisto PT, Kaakkola S (1999) Catechol-O-methyl-transferase (COMT). Biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors. Pharmacol Rev 51 593-628... 

Summary of Biopharmaceutic Studies and Associated Analytical Methods Summary of Clinical Pharmacology Studies Summary of Clinical Efficacy Summary of Clinical Safety Literature References Synopses of Individual Studies... 

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