Plasma measurement

Plasma Measure plasma Primary adrenal insufficiency low plasma aldosterone level. ... 

A. Bonetti, H. S. Bridge, A. J. Lazarus, E. F. Lyon, B. Rossi, and F. Scherb. Explorer X Plasma Measurements, Proceedings of the Third International Space Science Symposium, Space Research III, W. Priester (ed.), North-Holland Publ. Co., Amsterdam, The Netherlands, 1963, 540-552. 

It should be possible, however, to predict those drugs for which plasma measurements are likely to prove most useful. (1) The drug should show a more or less close correlation between its concentration in the plasma and its therapeutic effectiveness and/or toxicity (see below) (2) the disease for which the drug is used must be of sufficient duration to make... 

Polyatomic ion formation of REEs in different plasmas measured by LIMS, SSMS and... 

An ion-selective electrode responds to the activity of free analyte, not complexed analyte. For example, when the Pb2+ in tap water at pH 8 was measured with a sensitive ion-selective electrode, the result was [Pb2+] = 2 X 10 10 M.25 When lead in the same tap water was measured by inductively coupled plasma-mass spectrometry (Section 21-6), the result was more than 10 times greater 3 X 10-9M. The discrepancy arose because the inductively coupled plasma measures all lead and the ion-selective electrode measures free Pb2+. In tap water at pH 8, much of the lead is complexed by CO -, OH, and other anions. When the pH of tap water was adjusted to 4, Pb2+ dissociated from its complexes and the concentration indicated by the ion-selective electrode was 3 X 10-9M—equal to that measured by inductively coupled plasma. 

Experimental diabetes induced in rats with streptozotocin (60 mg/kg) decreased TAC of blood plasma (measured with Randox kit) after 1 week (by 8.5%) after 4 weeks of diabetes, control values of TAC were recovered. However, TAC measured by enhanced chemiluminescence (W10), which was much lower, did not change after 1 week and was higher than control value after 4 weeks of diabetes (by 85%) (F5). Experimental colitis induced in rats by intrarectal administration... 

First-Point Cmax. The first point of a concentration-time curve in a BE study based on blood and/or plasma measurements is sometimes the highest point, which raises a question about the measurement of true Cmax because of insufficient early sampling times. A carefully conducted pilot study may avoid this problem. Collection of an early time point between 5 and 15 min after dosing followed by additional sample collections (e.g., two to five) in the first hour after dosing may be sufficient to assess early peak concentrations. If this sampling approach is followed, data sets should be considered adequate, even when the highest observed concentration occurs at the first time point. 

Now, displacement, by increasing/, will increase CL (since CL f, CLint). But because the events within the cell are unaffected by displacement, it follows that CLint will not change and therefore neither will Cuss, the therapeutically important unbound concentration at steady state. Consequently, no change in response is expected. Indeed, had no plasma measurements been made, one would have been totally unaware that an interaction had occurred. Furthermore, if plasma measurements are made, it is important to determine the fraction of the unbound dmg and its free concentration otherwise, there is clearly a danger of misinterpretation of the interaction. 

LCAT in the rat appears to be produced by the liver (B48, Nil, Oil). Although there seems to be no direct evidence of production by the liver in man, the hepatic origin of LCAT is suggested by the marked reduction in LCAT activity associated with liver diseases (C23, S51) including viral hepatitis (B37, Til) and cirrhosis (B37, S2, S36). LCAT activity is also said to be reduced in uremia (Sll) and pancreatic carcinoma (S36). The concentration of LCAT in normal human plasma (measured by radioimmunoassay) is about 6 mg/liter (A8). 

After a drug is administered to the body it goes through various phases of distribution. If we were to make periodic plasma measurements of a drug following its administration, its plasma profile would be a composite of various dynamic processes serving to increase or decrease its concentration. The processes of distribution can be considered in terms of compartments. 

Fig. 5. Concentration of sulfur dioxide in an oxygen plasma measured by mass spectrometry vs. time during PBTMSS etching under various conditions. RIE (20 mTorr Oj 10 seem) A -320 V, B -350 V, C -380 V, D -450 V, E -550 V SME (20 mTorr, 10 seem Oj) F 50 W, G 100 W...

Results of isotope ratio measurements from an earlier study that used a similar protocol to the one just described are shown in Figure 3. These curves show plasma Isotope levels for both the i.v.oral tracer, labelled as PTA and CTA respectively. It is generally accepted that isotopic enrichment, atom percent excess, of urine reflects that of plasma, and after the initial period of rapid mixing, urinary atom percent excess is used in lieu of plasma measurements. The curves drawn through the data are those generated using the proposed model for calcium kinetics. 

The erosion rates of polymers in an oxygen plasma, measured by Rentzepis and coworkers,provided the first evidence that polymer degrar dation in an environment containing atomic oxygen is qualitatively different than thermal oxidation of a polymer by molecular oxygen. In thermal oxidation with O2, initiation must begin with spontaneous dissociation of a C-H or C-C bond, which forms a radical that can then react with molecular oxygen ... 

First the patient is given a small dose of radioactive vitamin Bj2 orally, with a simultaneous large dose of nonradioactive vitamin B intramuscularly. The large injected dose saturates binding sites so that any of the oral radioactive dose that is absorbed cannot bind and will be eliminated in the urine where it can easily be measured (normally > 10% of the administered dose appears in urine collected for 24 h, if renal function is normal). In pernicious anaemia and in malabsorption, gut absorption and therefore subsequent appearance of radioactivity in the plasma (measured 8-12 h later) and urine are negligible. 

A less important but interesting point is that many of the established and pharmacopoeia-listed excipients are not accompanied by strict standardized assay methods. In this situation, a new assay needs to be established by the company with the new drug formulation for characterization and/or plasma measurement of the excipient. 

This phenomenon is explained by the fact that intravenous immunoglobulin increases the non-aqueous phase of the plasma, resulting in a relative loss of plasma water volume. Sodium is virtually restricted to serum water, so each volume of plasma measured will contain less sodium and be interpreted as hyponatremia. Using a direct ion-selective electrode avoids this problem. 

Potassium is primarily an intracellular ion and, consequently, decreases in whole-body potassium may not be detected by plasma measurements (Muylle et al 1984). Although erythrocyte potassium content has been used to estimate whole-body potassium (Muylle et al 1984), its accuracy has not been validated. Moreover, the extracellular potassium concentration (reflected in the plasma) is critical for neuromuscular transmission and is, therefore, more relevant to clinical signs than whole-body potassium stores (Rose 1994). The intervention level for treatment of hypokalemia has not been established. In postoperative colic and proximal enteritis, where the prevention of ileus is a primary goal, it may be prudent to supplement if the plasma potassium concentration falls to <3.5mEq/l. In other situations, especially those being fed enterally, it may not be necessary to treat if the plasma potassium concentration is >3.0mEq/l. 

A variety of exogenous (radioisotopic and nonradioisotopic) and endogenous markers have been used to estimate clearance (Table 24-2). Measurement of clearance may require accurate measurements of both plasma and urinary concentrations of the marker used plus a reliable urine collection. For a reliable plasma measurement, the substance must have reached a steady-state concentration and not be rapidly changing. For a reliable urine collection, the urine flow must be adequate (several mL/min), the collection period of long enough duration, and complete bladder emptying achieved these requirements are problematic. 

Routine methods. In most cases, lipid and lipoprotein measurements can be made using specimens of either serum or plasma. Measurements in EDTA plasma can be converted to serum-equivalent values using the following equation ... 

Additional markers of catecholamine overproduction have been employed to improve the biochemical detection of neuroblastomas. Free dopamine may be abnormal in urine from neuroblastoma patients with VMA and HVA excretion. Combined testing for VMA, HVA, and dopamine may therefore improve tumor detection, and in 1993 an international consensus report on neuroblastoma diagnosis added dopamine to the Hst of acceptable measurements to document the adrenergic nature of the tumor. Plasma measurements of dopamine and L-dopa, the amino acid precursor of dopamine, may also have clinical value and allow the alternate use of plasma. Measurement of methylated metabolites, especially normetanephrine, has also been explored. When urinary normetanephrine, metanephrine, methoxytyra-mine, dopamine, norepinephrine, VMA, and HVA were measured, clinical sensitivity for detection of neuroblastomas was 97% to 100% when results of normetanephrine testing were coupled either with VMA in the infants or with HVA in children greater than age 1. Even with an extended panel of catecholamines and metabolite measurements, a low incidence of nonsecreting tumors continues to be identified and should be considered in the interpretation of a negative test result. 

Urinary catecholamines represent a quantitatively small but diagnostically important component of the catecholamine excretion products. Catecholamines are excreted in the urine as free amines and as glucuronide and sulfate conjugates. As with plasma measurements, total urinary catecholamines (conjugated and unconjugated forms) may be measured by... 

The methods described below require a spectrofluorometer fitted with a red-sensitive photomultiplier. If such equipment is not available locally, samples should be referred to a specialized laboratory because erythrocyte and plasma measurements are required rarely for the urgent assessment of acutely ill patients. 

CE Cook, E Amerson, WK Poole, P Lesser, L O Tuama. Phenytoin and phenobarbital concentration in saliva and plasma measured by radioimmunoassay. Clin Pharmacol Ther 18 742, 1975. 

H Brailly, et al. Total interleukin-6 in plasma measured by immunoassay. Clin Chem 40 116, 1994. 

The assay used by Pattnaik et al. (1978) to isolate the cholesteryl ester transfer protein in human plasma measured the transfer of 3H-labeled cholesteryl ester from low density to high density lipoprotein. The transfer reaction was terminated by adding MnC and centrifuging to sediment the low density lipoprotein. A heparin, MnCl2 precipitation step may also be used however, in the presence of a phosphate buffer, heparin is not necessary for precipitation of low density lipoprotein. Routine assays were found to be reproducible to within 10%. The increase in high density lipoprotein radioactivity is linear with time until about 25% of the initial low density lipoprotein radioactivity is transferred. The lipoproteins may also be separated by ultracentrifugation. When these two methods were compared, the results agreed within 10%. The precipitation technique is much faster (less than 15 min compared with 18 hr) and simpler. 

Matsuyama, H., Ruhmann Wennhold, A., Johnson, L.R., and Nelson, D.H. (1972) Disap pearance rates of exogenous and endogenous ACTH from rat plasma measured by bioassay and radioimmunoassay. Metabolism, 21, 30 35. 

Radioimmunoassay (RIA) is the method most commonly used for the measurement of plasma and urinary concentrations of GST. The first RIA described for the GST was for rat ligandin (GST YaYa) (B6) and in 1978 the first assay for human ligandin was described (T13). The assay for human ligandin lacked sensitivity as did the RIA for human ligandin described in 1983 by Sherman et al. (H18, S20). In 1984 we described the first RIA methods that could differentiate the B1 and B2 subunits with a high degree of sensitivity and specificity as shown in Table 9 (B16). These assays could detect both the upper and the lower reference limits for plasma measurements. When animals were immunized with the homodimer B,B or B2B2, the cross-reactivity that the antisera had with the heterodimer B,B2 was quite variable. Because the proportion of the B,B2 heterodimer in liver can vary markedly (H63), it is important to choose antisera that will react only with one of the subunits in the heterodimer. The antisera we used for our subsequent clinical studies on plasma Bj and Bj subunit measurements in plasma or serum exhibited approximately 50% cross-reactivity with the B,B2 heterodimer and thus it was possible to measure total B, or B2 subunits rather than the total subunits in the homodimer and a variable proportion of the same subunit in the homodimer. 

The previous section explained how to estimate plasma concentrations based on known PK parameters for a drug this section provides the methods for estimating the PK parameters of a drug based on experimental plasma measurements. The data analysis methods for each model have some steps in common, but each also contains calculations specific to the given model. 

The AUC can alternatively be estimated by applying the trapezoidal rule to sequential pairs of measured plasma concentration values, as illustrated in Figure 10.38. Calculation of the slice of AUC between time zero and the first plasma measurement, AUC O ti), is different from the bolus IV case since the initial concentration (Cq) is zero, giving... 

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