Range of plasma

From the comparison by Nyman et al. between plasma Hp level and different red cell destruction indices (half-life of CrB1-tagged erythrocytes, endogenous CO formation, stercobilin (urobilin) excretion in feces) it is evident that anhaptoglobinemia is a very common, but not an invariable accompaniment of increased red cell turnover. The exceptions are possibly persons with increased Hp synthesis. Individual differences in efficiency to destroy red cells outside the circulation without Hb return may be reflected by the wide normal variation range of plasma Hp as well by the promptness with which anhaptoglobinemia develops on even slight increase in Hb turnover. 

Metabonomics has changed the way data are analyzed. Instead of the single biomarker concept, the goal is to simultaneously measure the entire range of plasma metabolites to see changes in the patterns of the biomarkers. This requires both analytical platforms that can assess the broad range of metabolites in an individual and the knowledge of metabolism that is necessary to interpret the analytical data. 

Unfortunately, few of the studies that have attempted to relate the blood concentrations of neuroleptics to therapeutic response have fulfilled all these criteria. There is a suggestion that a "thera peutic window" exists for some phenothiazine neuroleptics. A therapeutic window is a range of concentrations of a drug measured in the blood that are associated with a good therapeutic response. Plasma concentrations outside this range are either too low to ensure a therapeutic response or so high that they induce toxic side effects. Despite the numerous studies of the relationship between the plasma concentration and the therapeutic response for a number of "standard" neuroleptics, it would appear that such correlations rarely account for more than 25% of the variance in clinical response to treatment. The existence of a therapeutic window for neuroleptics would therefore appear to be unproven. However, there could be ranges of plasma concentrations associated with optimal antipsychotic action, but these... 

Chromatographic procedures have been applied increasingly in the fractionation and purification of plasma lipoproteins (Bll, L3, W2). Agarose media have proved to be particularly valuable because of their sieving properties for particles in the size range of plasma lipoproteins, including the low- and very low-density classes (SI). 

Mania (divalproex sodium delayed-release tablets) 750 mg/day in divided doses increase as rapidly as possible to achieve the lowest therapeutic dose that produces the desired clinical effect or the desired range of plasma concentrations (trough plasma concentrations 50 to 125 mcg/mL). Maximum concentrations generally were achieved within 14 days. Maximum recommended dosage is 60 mg/kg/day. 

Too little drug at the effector site means no therapeutic effect, too much may cause toxic effects to appear. So there is commonly a range of plasma concentrations between which the desired effect is obtained without toxicity - often called the therapeutic window or therapeutic range (Fig. 5). 

While large interindividual variability in the steady-state plasma concentrations among patients treated with similar doses of a given antipsychotic is well established, the existence of a critical range of plasma concentration for therapeutic response or significant adverse effects remains controversial. A body of data from a number of fixed-dose studies, however, indicates a possible threshold for response or a linear or curvilinear relationship between plasma levels and clinical response for agents such as ... 

Table 3.7.2. shows the mean SD and (range) of plasma biotinidase activities as well as the activity ratio with 1.5 mM and 0.15 mM substrate obtained in our laboratory. The values in normal individuals (age 2 months to adult) are used as reference values, with the mean activity in the presence of 0.15 mM substrate used as the 100% value in calculations. These plasma samples were stored at - 20°C and assayed within 1 day to 2 months. Since mutation analyses were not performed, these controls may include individuals heterozygous for a mutation in the biotinidase gene. 

The heptane extraction efficiency from plasma was highly reproducible over a wide range of plasma concentrations - 100 ng/ml) 90.6 0.7% (SEM). 

The recovery of 1 from the heptane extract of dog plasma by normal phase HPLC was reproducible over the range of plasma concentrations studied. Equivalent overall recoveries were obtained by both radiochemical analysis (83.7 1.8% SE) and electron-capture GLC analysis (84.0 4.9% SE) of the derivatized tetrahydrocannabinol. ... 

Most of the experiments have been performed on He-like ions. This is due to the large range of plasma temperatures, where the fractional abundance is dominated by He-like ions, and in addition they are ideal for the diagnostics of hot plasmas. On the one hand, the spectra of He-like ions are rather simple to be calculated accurately, on the other hand, they are complicated... 

The plasma concentration of calcidiol is the most sensitive and usefiil index of vitamin D status, and is correlated with elevated plasma parathyroid hormone and alkaline phosphatase activity (Table 3.4). As shown in Table 3.2, the reference range of plasma calcidiol is between 20 to 150 nmol per L, with a twofold seasonal variation in temperate regions. Concentrations below 20 nmol per L are considered to indicate impending deficiency, and osteomalacia is seen in adults when plasma calcidiol falls below 10 nmol per L. In children, clinical signs of rickets are seen when plasma calcidiol faUs below 20 nmol per L. The plasma concentration of calcitriol does not give a useful indication of vitamin D status. The reference range is between 38 to 144 pmol per L and is maintained because of the stimulation of calcidiol 1-hydroxylation by parathyroid hormone secreted in response to faUing concentrations of calcium (Holick, 1990). 

The normal range of plasma concentrations of vitamins Dj and is 1 to 2 ng/ml, 25-HydK3xy itamin P3 is the form of the vitamin present at highest concentrations, with normal values ranging from 8 to 40 ng/mJ, A value of 12 ng/ml has been used as a cutoff point to indicate itamin D deficiency, though some clinicians have used lower levels to indicate vitamin D deficiency. The hormonally active form of the vitamin, l,25-(OH)jD occurs at much lower levels (15-45 pg/ml). 

Fig. 2 illustrates a utility curve, that is, a curve describing the clinical utility of a drug in terms of the risk of side effects from a high concentration and the risk of no effect from a low concentration. The closer the effect and toxicity curves, the more narrow is the range of plasma concentrations that can be used for therapy. The utility is obtained as the difference between the effect and toxicity. 

Drug Dog Human Therapeutic range of plasma concentrations (pg/ml)... 

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