Clinical steady state

Although it takes >711/2 to reach mathematical steady state, by convention clinical steady state is accepted to be reached at 4r-5 t1/r... 

To achieve clinical steady state usually takes approximately 5 X half-life. 

Fluorescence. The fluorescence detection technique is often used in clinical chemistry analyzers for analyte concentrations that are too low for the simpler absorbance method to be appHed. Fluorescence measurements can be categorized into steady-state and dynamic techniques. Included in the former are the conventional simultaneous excitation-emission method and fluorescence polarization. 

At low doses, both psychostimulants could theoretically stimulate tonic, extracellular levels of monoamines, and the small increase in steady state levels would produce feedback inhibition of further release by stimulating presynaptic autoreceptors. While this mechanism is clearly an important one for the normal regulation of monoamine neurotransmission, there is no direct evidence to support the notion that the doses used clinically to treat ADHD are low enough to have primarily presynaptic effects. However, alterations in phasic dopamine release could produce net reductions in dopamine release under putatively altered tonic dopaminergic conditions that might occur in ADHD and that might explain the beneficial effects of methylphenidate in ADHD. 

Following initial assessment, including evaluation of potential suicidality, support systems, and need for inpatient versus outpatient treatment, MW was hospitalized briefly, then followed in the community on medication along with psychotherapy. She has abstained from illicit substances and has returned to her job. She has responded well to treatment with sustained-release lithium carbonate 900 mg once daily at bedtime with a snack. Steady-state 12-hour serum lithium concentrations have stabilized at 0.9 mEq/L (0.9 mmol/L). She now returns to clinic for routine followup. She has tolerated the lithium except for a mild tremor and a gain of 7 pounds (3.2 kg). She is willing to accept these side effects for now, but asks about how long she must take medication since she is now feeling well. 

Yang, C., Zhao, J. P., Liu, B. et al. (2002). Relationships between clozapine steady-state concentration CYP1A2 activity and clinical response in schizophrenic patients. Journal of Chinese Psychiatry, 35(4), 202-5. 

The product specification should include a measure of uniformity of content and a dissolution test following the release of the active ingredient until steady state is achieved (or justifying shorter periods of testing). Where possible, the dissolution specification (often expressed as quantity of active ingredient released per unit area of surface per unit time) should be related to the results obtained from batches found to be acceptable in clinical studies. In these tests six units should be tested for dissolution characteristics and the mean value stated with a measure of variability. 

Also, we have noted that patients with unilateral cataracts after trauma or retinal detachment repair typically have very similar RRS carotenoid levels in the normal and in the pseudophakic eye. Thus, we have concluded that there is a decline of macular carotenoids that reaches a low steady state just at the time when the incidence and prevalence of AMD begins to rise dramatically. While this age effect has been noticed sometimes also in other studies using clinical populations and different MP detection methods (Sharifzadeh et al. 2006, Nolan et al. 2007), several groups have reported constant, age-independent MP levels. Examples include reflectance-based population studies in which respective average MP optical densities of 0.23 (Delori et al. 2001), 0.33 (Berendschot et al. 2002), and 0.48 (Berendschot and Van Norren 2004) were determined. 

Elevated ET-1 in SCA patients, even in the steady state, may play an important role in the dehydration of sickle erythrocytes and the resulting enhanced intra-erythrocytic HbS polymerization. Indeed, it has been shown that ET-1 activates Ca2+- gated K+ channels in mouse erythrocytes [34]. ET-1, as a pro-inflammatory agonist, has been shown to induce the production of inflammatory cytokines by monocytes. One of the cytokines, namely TNFa enhances the adherence of sickle erythrocytes to vascular endothelium [35]. In addition, endothehns upregulate the expression of endothelial adhesion molecules such as ICAM-l, VCAM-1 and E-se-lectin, which participate in the recruitment of white cells to the site of inflammation. The overall conclusions that can be drawn from these data is that ET-1 plays a critical role in the vasospasm and inflammation that result in VOC. The major effect of HU in ameliorating the clinical symptoms of SCA likely results from its ability to inhibit the chronically activated ET-1 expression in SCA patients. 

For clinical chemistry the most important question is whether or not changes in enzyme activity will accompany defined disease states, the materials being obtainable by ways practicable in clinical medicine. The enzyme levels of G-6-PDH and 6-PGDH are assayed in serum, blood (hemolyzates), and liver homogenates yielded by biopsy. In the latter case it is necessary most of all to take account of the probable differences between the assay conditions and the steady state. Furthermore, the reference system is of decisive importance (e.g., cellularity... 

Ishida, M., Otani, K., Kaneko, S., Ohkubo, T., Osanai, T., Yasui, N., Mihara, K., Higuchi, H. and Sugawara, K. (1995) Effects of various factors on steady state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine. International Clinical Psychopharmacology, 10 (3), 143-146. 

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