Therapeutic Windows

The threshold dose of MDMA is 30 mg, but the average dose is 80-150 mg, with some users taking in excess of 200 mg. The lethal dose is estimated (from animal data) to be approximately 6,000 mg. On the street, concentrations of MDMA can vary greatly, and tablets may also contain other substances such as methylenedioxyamphetamine (MDA) and methylenedioxy-ethylamphetamine (MDEA) (Sherlock et al. 1999). The presence of these other substances is often associated with emergency presentations because of their narrower therapeutic windows. 

The efficacy of IV thrombolysis in patients with moderate-to-severe strokes due to proximal arterial occlusions is restricted by several factors, including the relatively short therapeutic window, poor recanalization rates as the clot burden increases, restrictive eligibility criteria, and the risk of intracerebral hemorrhage. Endovascular techniques improve the rates of recanalization in this patient population, and appear to increase the likelihood of a good functional outcome. Intravenous thrombolysis... 

Belayev L, Liu Y, Zhao W, Busto R, Ginsberg MD. Human albumin therapy of acute ischemic stroke marked neuroprotective efficacy at moderate doses and with a broad therapeutic window. Stroke 2001 32 553-560. 

Markarian GZ, Lee JH, Stein DJ, Hong SC. Mild hypothermia therapeutic window after experimental cerebral ischemia. Neurosurgery 1996 38 542-550 [discussion 551]. 

Lou M, Eschenfelder CC, Herdegen T, Brecht S, Deuschl G. Therapeutic window for use of hyperbaric oxygenation in focal transient ischemia in rats. Stroke 2004 35 578-583. 

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... 

Drugs, among all the environmental factors that we are exposed to, may be particularly likely to interact specifically and selectively with the genetic properties of a given individual, as their potency pitches them into a narrow therapeutic window , precariously balanced between potent potions and perilous poisons. We would predict that, based on a patients innate, individual biological makeup -as it affects the interaction with a drug - one or the other of these properties may manifest itself this phenomenon is covered by the term pharmacogenetics. 

The photophysical properties of magnesium(II) tetra-(i-butyl)phthalocyanine (27) have been studied in solution, in micelles and in liposomes cation radical formation (CBr4 as electron acceptor) has been detected with UV excitation, or by a two-photon excitation using a pulsed laser in the therapeutic window at 670 nm.118 The Mg11 complex of octa(tri-z -propylsilylethy-nyl)tetra[6,7]quinoxalinoporphyrazine (28) has been prepared as a potential PDT sensitizer. The synthesis is shown in Figure 8. Compound (28) has Amax 770 nm (e = 512,000 M-1 cm-1), d>f = 0.46 and d>A = 0.19 (all in THF, under air).119... 

The development of new synthetic methodology has successfully enabled the investigation of structure-activity relationships (SAR) of perylenequinone agents for use in photodynamic therapy. Simplified analogs, such as (M)-96, that have potency equal to the natural product hypocrellin and superior chromophores to improve photoactivation in the therapeutic window were prepared. 

In acutely depressed patients, there is a correlation between antidepressant effect and plasma concentrations for some TCAs. Table 70-3 shows suggested therapeutic plasma concentration ranges. The best-established therapeutic range is for nortriptyline, and data suggest a therapeutic window. 

Rao et al.20 demonstrated a fluorescence polarization immunoassay for evaluating serum concentrations of tricyclic antidepressants (amitriptyline, imipramine, clomipramine, and doxepin) with respect to nonresponse, compliance, therapeutic window, and influences of age, sex, substance abuse, and toxicity. Abbott Laboratories TDx/TDxFLx Toxicology Tricyclic Assay FPIA (fluorescence polarization immunoassay) was used. This assay of 50 /uL samples contained tricyclic antidepressant antibodies raised in rabbits and fluorescein-labeled tricyclic antidepressant as a tracer. The assay was calibrated with imipramine in the range of 75 to 1000 fig/L (268 to 3571 nmol/L). Intra-assay and inter-assay coefficients of variation for internal quality control samples from the manufacturer were 4.2 and 4.7%, respectively. The limits of detection were 72,71,64, and 72 nmol/L for amitriptyline, imipramine, clomipramine, and doxepin, respectively. This high-throughput immunoassay was easy to use although amitriptyline, dosulepine, desipramine, and nortriptyline showed cross-reactivities ranging from 74 to 100%. 

Therapeutic window. This term is applied to the difference between the minimum and maximum doses that may be given patients to obtain an adequate clinical response and avoid intolerable toxic effects. The greater the value calculated for... 

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