Therapeutic time window

The neuroprotective effects of other compounds have also been demonstrated to be enhanced when combined with hypothermia. Guan et al. (6) evaluated the efficacy of hypothermia in combination with insulinlike growth factor (IGF) using a modified Levine hypoxic-ischemic model (right carotid ligation plus 10 min of hypoxia in neonatal animals). In this study, the use of hypothermia resulted in a significant extension of the therapeutic time window. Recovery in a cool vs a warm environment (23 C vs 31 C) extended the effectiveness of IGF-1 by up to 4 h. 

Around acutely infarcted brain, there is an ischemic penumbra (Astrup et al. 1981). Here the blood flow is low, function depressed and the oxygen extraction fraction high. In other words, there is viable tissue with misery perfusion where the needs of the tissue are not being met The tissue may die or recover, depending on the speed and extent of restoration of blood flow. This concept opens up the possibility of a therapeutic time window during which restoration of flow or neuronal protection from ischemic damage might prevent both immediate cell death and the recruitment of neurons for apoptosis (see Ch. 21). 

Fig. 1 Using a T-piece between HPLC and MS, a syringe pump can be utilized to infuse a constant flow of analytes at therapeutic concentrations whilst drug spiked whole blood samples are delivered via SPE-HPLC. Ion traces of the analytes (here everolimus at 6 ng/ml) are recorded. In this particular case, no ion yield attenuation due to the spiked drug can be observed, although strong effects can be seen in the solvent front elution zone shortly prior to the analyte elution time window...

A critical factor in developing a therapeutic strategy against stroke is the time window available. In focal cerebral ischemia, delaying the... 

Finally, it should be cited the possibility to use GL microspheres as temperature-cured dissolvable therapeutic cell carriers. GL microspheres dissolve completely in a time window of 2 days at 37°C (Leong et al., 2013). 

Response fluctuations occur with disease progression as the patient s dopamine reserves are depleted in the brain and as a complication of PD treatment. Motor fluctuations include delayed peak response, early wearing off, random unpredictable on-off, and freezing. Dyskinesias include chorea, dystonia, and diphasic dyskinesia. Wearing off can be visualized by imagining the therapeutic window of dopamine narrowing over time. The therapeutic window is defined as the minimum effective concentration of dopamine required to control PD symptoms (on without dyskinesia) and the maximum concentration before experiencing side effects from too much dopamine (on with dyskinesia). Early in the disease, a dose of... 

Figure 12.1 shows the plasma concentration versus time profile of an orally administered hypothetical drug. When the drug concentration in plasma equals the minimum effective concentration (MEC), therapeutic response is initiated. When the concentration exceeds the minimum toxic concentration (MTC), the drag causes toxic responses. Therefore, for ideal therapeutic response, the plasma concentration of drugs should be between the MEC and MTC. This region is called the therapeutic window. In Figure 12.1 the MEC is 1.5 ng/ mL, and the MTC is 3.5 ng/mL. The therapeutic window is between 1.5 and 3.5 ng/mL. 

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