Pharmaceuticals therapeutic index

The analysis of the contribution made by increased pharmaceutical spending to the growth in the per capita intensity of health resources suffers from major measurement problems that deprive available indicators of any value. Traditional pharmaceutical price indexes (such as the Laspeyres index, used to calculate the pharmaceutical component of the consumer price index) provide little relevant information in a market in which the introduction of therapeutic innovations is of prime importance the indexes show an apparent freeze, and sometimes even a steep drop (as in the Spanish case). However, the steady rise in the average price per prescription paints a very different picture. 

Using wortmannin as a model, broad-spectrum PI3K inhibitors with improved pharmaceutical properties and therapeutic indexes have been reported in recent pubhcations. PWT-458 (compound 10, Fig. 3), which is a pe-gylated derivative of wortmannin, was shown to inhibit PI3K signaling and hold a higher therapeutic index over its parent compoimd when used in sev-... 

Extrapolations of therapeutic index and toxicity data from animals to humans are reasonably predictive for many but not for all toxicities. Seeking an improved process, a Predictive Safety Testing Consortium of five of America s largest pharmaceutical companies with an advisory role by the Food and Drug Administration (FDA) has been formed to share internally developed laboratory methods to predict the safety of new treatments before they are tested in humans. In 2007, this group presented to the FDA a set of biomarkers for early kidney damage. 

Various factors affect the reproducibility of drag delivery to the lungs, including physiological (respiratory maneuver) and pharmaceutical (device, formulation) variables. For the systemic delivery of drags with a narrow therapeutic index, such variations may be unacceptable. 

The therapeutic range is a range of dosage that is safe to administer to a patient based on the therapeutic index. This range is also known as the therapeutic window. The therapeutic range is defined as between the minimum effective concentration (MEC) for achieving the pharmaceutical response and the minimum toxic concentration (MTC). 

Pharmaceutical products containing an API with a narrow therapeutic index should always be tested with in vivo methods, because the risk to the patient resulting from a possible incorrect bioequivalence decision using the biowaiver procedure is considered too high with these kinds of APIs. 

The decision of a national authority to allow a biowaiver based on the BCS should take into consideration the solubility and permeability characteristics as well as the therapeutic use and therapeutic index of the API, its pharmacokinetic properties, the similarity of the dissolution profiles of the multisource and the comparator products in standard buffers with a pH of 1.2, pH 4.5 and pH 6.8 at 37 °C. Data related to the excipients composition in the multisource product are also required. A systematic approach to the biowaiver decision has been established by the International Pharmaceutical Federation (FIP) and published in the Journal of Pharmaceutical Sciences (http //www3.interscience.wiley.com/cgi-bin/jhome/68503813). The relevant documents can also be downloaded from the FIP web site at http //www.fip.org/. These monographs provide detailed information which should be taken into account whenever available in the biowaiver consideration. 

However, in the 21st century, the ethical pharmaceutical industry has been fully geared towards the production of relatively safer, less toxic, more effective, higher therapeutic index, novel, innovative medicaments that will evidently help the mankind to afford a disease-free society besides, the elder ones with a glaring hope to live a still longer life span. 

The initial focus, at that time, for drugs as well as the other two types of ingested or topically applied products, was lack of contamination as determined by quality sampling and testing. In addition, and extrapolating that issue to new proposed pharmaceuticals, the key data required was the toxicity data and its ratio to the proposed dose level, the therapeutic index. However, no data or judgment on efficacy was required for its proposed use. Its medical purpose and its ultimate use remained in the hands of the physician and the sponsoring company that promoted it. 

Most drug delivery systems currently used to treat pulmonary disease were developed and introduced into clinical practice long before assessments of pulmonary drug delivery were undertaken. The pharmaceutical companies have seen little reason to improve on the current devices, utilizing technology that is many decades old, because the current systems do produce useful therapeutic responses and are relatively safe ( therapeutic index ) if used effectively. 

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