Serum concentration, determination

Lithium is easily, inexpensively, and accurately measurable in the serum, and serum concentration determination is a useful adjunct to monitoring its therapeutic efficacy and avoiding toxicity (54). 

Sample size and timing of blood drawing for serum concentration determination... 

CL Dougherty, J Kres, H Davoudi. Bio availability studies of drugs with nonlinear pharmacokinetics. II. absolute bioavailability of intravenous phenytoin prodrug at therapeutic phenytoin serum concentrations determined by doublestable isotope technique. J Clin Pharmacol 33 89-94, 1993. 

If the patient is not at steady state, an additional postdose serum concentration determination should be done to compute the patient s pharmacokinetic parameters. Ideally, the third concentration (C3) should be acquired approximately one estimated half-life after the postdose maximum concentration. Determining serum concentrations too close together will hamper the drug assay s ability to measure differences between them, and getting the third sample too late could result in a concentration too low for the assay to detect. In this situation, the predose minimum and postdose maximum concentrations are used to compute V, and both postdose concentrations are used to calculate fi/2 (Fig. 5-11). 

Noncatalytic Reactions Chemical kinetic methods are not as common for the quantitative analysis of analytes in noncatalytic reactions. Because they lack the enhancement of reaction rate obtained when using a catalyst, noncatalytic methods generally are not used for the determination of analytes at low concentrations. Noncatalytic methods for analyzing inorganic analytes are usually based on a com-plexation reaction. One example was outlined in Example 13.4, in which the concentration of aluminum in serum was determined by the initial rate of formation of its complex with 2-hydroxy-1-naphthaldehyde p-methoxybenzoyl-hydrazone. ° The greatest number of noncatalytic methods, however, are for the quantitative analysis of organic analytes. For example, the insecticide methyl parathion has been determined by measuring its rate of hydrolysis in alkaline solutions. 

Amylase enters the blood largely via the lymphatics. An increase in hydrostatic pressure in the pancreatic ducts leads to a fairly prompt rise in the amylase concentration of the blood. Neither an increase in volume flow of pancreatic juice nor stimulation of pancreatic enzyme production will cause an increase in senm enzyme concentration. Elevation of intraductal pressure is the important determinant. Stimulation of flow in the face of obstruction can, however, augment the entry of amylase into the blood, as can disruption of acinar cells and ducts. A functional pancreas must be present for the serum amylase to rise. Serum amylase determination is indicated in acute pancreatitis in patients with acute abdominal pain where the clinical findings are not typical of other diseases such as appendicitis, cholecystitis, peptic ulcer, vascular disease or intestinal obstruction. In acute pancreatitis, the serum amylase starts to rise within a few hours simultaneously with the onset of symptoms and remains elevated for 2 to 3 days after which it returns to normal. The peak level is reached within 24 hours. Absence of increase in serum amylase in first 24 hours after the onset of symptoms is evidence against a diagnosis of acute pancreatitis (76). 

Serum concentrations of PCP determined by enzyme immunoassay in 405 patients also did not correlate with the state of intoxication at the time the blood speciman was obtained, although the highest PCP concentrations in the study were associated with major patterns. However, some patients with major patterns had negative... 

In patients with a history of AED use, a baseline serum concentration may be useful to determine if the drug concentration is below the desired range and if a loading dose is needed. Albumin levels, renal function tests, and liver function tests can also be helpful when assessing antiepileptic therapy. 

Assess the AED serum concentration and adjust therapy as needed for agents with a defined therapeutic range (e.g., phenytoin, carbamazepine, valproic acid, and phenobarbital). Drug levels can also be used to determine adherence to medication regimens for agents that do not have defined ranges. 

Effectiveness of TB therapy is determined by AFB smears and cultures. Sputum samples should be sent for AFB staining and microscopic examination (smears) every 1 to 2 weeks until two consecutive smears are negative. This provides early evidence of a response to treatment.28 Once on maintenance therapy, sputum cultures can be performed monthly until two consecutive cultures are negative, which generally occurs over 2 to 3 months. If sputum cultures continue to be positive after 2 months, drug susceptibility testing should be repeated, and serum concentrations of the drugs should be checked. 

PSA determination can be used to investigate the necessity for a prostate biopsy. PSA is considered a useful analyte in the diagnosis and management of prostate cancer however, increased serum concentrations of PSA are also seen in patients without cancer of the prostate (e.g., patients with bacterial prostatitis or benign... 

For penicillin-allergic adults, use a fluoroquinolone (ciprofloxacin 0.5-0.75 g orally every 12 hours or 0.4 g IV every 12 hours levofloxacin 0.5-0.75 g orally or IV every 24 hours or moxifloxacin 0.4 g orally or IV every 24 hours). eGentamicin or tobramycin, 2 mg/kg loading dose, then maintenance dose as determined by serum concentrations, fluoroquinolone or aztreonam 1 g IV every 6 hours may be used in place of the aminoglycoside in patients with severe renal dysfunction or other relative contraindications to aminoglycoside use. 

CH50 determinations can be used to analyze the total serum complement and are useful for monitoring immune complex diseases (Sullivan, 1989) activation of complement (Table 15.13) in the presence of autoantibodies is indicative of immune complex diseases and autoimmunity. The various components of the complement system (C3, C4) can also be measured to assess the integrity of the system. For instance, low serum concentrations of C3 and C4, with a concomitant decrease in CH50 may indicate activation of complement, while a low C4 alone is a sensitive indicator of reduced activation of the complement system. Since C3 is used as an alternate complement pathway, it usually measures high. Therefore, a low C3 with a normal C4 may indicate an alternate pathway of activation. 

It may be important to determine the degree of plasma protein and red blood cell binding of the test substance calculation of blood clearance rates using plasma or serum concentrations of the substance that have not been adjusted for the degree of binding may under or over-estimate the true rate of clearance of the test substance from the blood. This is usually done through experiments in vitro. 

The situation with the sulfonamides is quite different than with many of the antibiotics. In this instance the correlation between attainment of vitro inhibitory concentration requirements as vivo serum concentrations and drug efficacy has not been as good as with most of the antibiotics. As a result, a general recommendation of 50 ug/ml of drug in serum has been widely accepted as the desirable concentration for all the sulfonamides. Unfortunately little effort has been expended in veterinary medicine to determine MIC relationships between various bacteria and sulfonamides (6). 

Age or body weight can affect the systemic availability of many antimicrobial agents. In the physically smaller animal (sheep and pig) the peak serum concentration of a drug is usually higher and is followed by a rapid decline compared with a lower peak and a slower decline of the antibiotic in seruon of the larger animal (cow and horse). The limited experimental data appear to indicate that the extent of systemic availability of IM-administored antibiotics can vary as widely between different sites as between IM and SC sites. A corollary to this observation is that the location of the extra-vascular injection site should be well-defined when determining the systemic availability of parenteral preparations (9). 

Other antibiotics studied using RPC include chloramphenicol which could be determined at serum concentrations of about 0.5 /xg/ml using 0.1 ml samples ( 15) after extraction with ethyl acetate (316). A simple method for the analysis of chloramphenicol in serum and cerebrospinal fluid has been reported in which the analyte is extracted into methanol and the extract chromatographed with acetic acid-water methanol (1 62 37) as the mobile phase (i/7). 

The absolute concentration of blood-derived proteins is modulated by the CSF flow rate. In general, the actual CSF protein concentration is determined by the following variables individual serum concentration and individual diffusion pathway, age, site of puncture, and volume of extraction. 

Concentration of transferrin in CSF does not correlate with serum levels. This suggests consideration of the presence of a speciflc transport system for transferrin in the blood-CSF barrier. This transport system may be similar to that, for instance, for immunoglobulins (transcytosis). Only as an epiphenomenon is there a signiflcant decrease of serum concentrations of transferrin, as in cases of ulcerous meningitis and malignant meningeal inflltration. In this case other methods are required to determine the levels with any degree of precision (A24, Zl). 

Quantitative methods are based on the determination of the concentrations of IgG and albumin correspondingly in cerebrospinal fluid and in serum. This way, it is possible to differentiate the increased concentration of IgG in CSF, which is based on the penetration of this protein from serum under the conditions of increased serum concentrations or failure of the blood-CSF barrier (Reiber s formulas see Section 3.2.3). 

During the monitoring of any protein in cerebrospinal fluid, it is necessary to bear in mind the functional status of the blood-CSF barrier, serum concentration of the respective protein, and the dimensions of the molecule (or the information based on the molecular weight). These data principally influence the resulting concentration in cerebrospinal fluid. It must also be emphasized again that the parallel determination of albumin in cerebrospinal fluid and serum is necessary. 

---