Serum levels

LIPOPROTEINS. Blood plasma lipoproteins are prominent examples of the class of proteins conjugated with lipid. The plasma lipoproteins function primarily in the transport of lipids to sites of active membrane synthesis. Serum levels of low density lipoproteins (LDLs) are often used as a clinical index of susceptibility to vascular disease. 

Replacement of the methyl ketone moiety in 78 by a phenyl sulfoxide, interestingly, leads to a relatively potent uricosuric agent with diminished antiinflammatory action. This effect in lowering serum levels or uric acid leads to the use of this drug in the treatment of gout. Alkylation of diethyl malonate with the chlorosulfide, 79, gives the intermediate, 80. The pyrazolodione (81) is prepared in the usual way by condensation with hydrazobenzene. Careful oxidation of the sulfide with one equiv-... 

MMI and PTU can lead to methimazole embryopathy with choanal or esophageal atresia. In pregnant women the antithyroid diug dose should be minimized to prevent fetal hypothyroidism by maintaining the maternal free thyroxine serum level slightly above the upper limit of normal. 

Leptin is a cytokine produced and secreted by adipose tissue in proportion to the body fat content [3]. Mice and humans lacking leptin or its receptor develop a severe hyperphagia and a dramatic degree of obesity which is considerably more pronounced than that of the NDRKO mouse. Thus, leptin is the key adiposity signal in rodents and humans. Leptin secretion appears to reflect the metabolic status of the adipocyte rather than the sheer size of triglyceride deposits, and leptin levels may transiently be dissociated from total body fat. Nonetheless, over the course of a day with unrestricted food supply, plasma leptin levels reliably reflect the amount of total body fat. Local administration of leptin into the brain results in reduced food intake. The vast majority of patients with obesity have elevated serum levels of leptin. Thus, it is believed that the polygenic obesity is due to leptin resistance rather than to inadequate leptin secretion, or to a reduced blood/brain transport of the cytokine. 

Intestinal absorption of digoxin is less complete compared to digitoxin. In order to improve absorption, acetylated- and methylated-digoxin derivates were developed. Digitoxin is metabolised in hepatic microsomal enzymes and can be cleared independently from renal function. The therapeutical serum level of digoxin is 0.5-2.0 ng/ml and 10-35 ng/ml of digitoxin. Steady state plateau of therapeutic plasma concentrations is reached after 4-5 half-life-times using standard daily doses [5]. 

Additional PPAR5 effects f Serum levels of apoA-l and apoA-ll (components of HDL-C) ft Circulating HDL-C concentrations13... 

Kunin CM (1967) A guide to use of antibiotics in patients with renal disease. A table of recommended doses and factors governing serum levels. Ann Intern Med 67 (1 ) 151—158... 

Use of the macrolides increases serum levels of digoxin and increases the effects of anticoagulants. Use of antacids decreases the absorption of most macrolides. The macrolides should not be administered with clindamycin, lincomycin, or chloramphenicol a decrease in the therapeutic activity of the macrolides can occur. Concurrent administration of the macrolides with theophylline may increase serum theophylline levels. 

When either drug is administered with diuretics and other hypotensives, an increased hypotensive effect may occur. When labetalol is administered with cimetidine, the effects of labetalol are increased. Halothane increases the effects of labetalol. When carvedilol is administered with the antidiabetic drugs, there is an increased effectiveness of the antidiabetic drugs. There is an increased effectiveness of clonidine when carvedilol is administered with clonidine There is an increased serum level of digoxin when digoxin is administered with carvedilol. 

When carbamazepine is administered with primidone, decreased primidone levels and higher carbamazepine serum levels may result. Cimetidine administered with carbamazepine may result in an increase in plasma levels of carbamazepine that can lead to toxicity. Blood levels of lamotrigine increase when the agent is administered with valproic acid, requiring a lower dosage of lamotrigine... 

The effects of buspirone are decreased when the drug is administered with fluoxetine Increased serum levels of buspirone occur if the drug is taken with erythromycin or itraconazole Should any of these combinations be required, the dosage of buspirone is decreased to 2.5 mg BID, and the patient is monitored closely. Venlafaxine blood levels increase with a risk of toxicity when administered witii MAOIs or cimetidine There is an increased risk of toxicity when trazodone is administered with the phenothiazines and decreased effectiveness of trazodone when it is administered with carbamazepine Increased serum digoxin levels have occurred when digoxin is administered with trazodone There is a risk for increased phenytoin levels when phenytoin is administered witii trazodone... 

LITHIUM The dosage of lithium is individualized according to serum levels and clinical response to the drug. The desirable serum lithium levels are 0.6 to 1.2 mEq/L Blood samples are drawn immediately before die next dose of lithium (8-12 hours after the last dose) when lithium levels are relatively stable During die acute phase die nurse monitors serum lithium levels twice weekly or until die patient s manic phase is under control. During maintenance therapy, the serum lidiium levels are monitored every 2 to 4 months. 

Remember that frequent monitoring of theophylline serum levels is important. 

Serum levels (digoxin) may be ordered daily during the period of digitalization and periodically during maintenance therapy. Periodic electrocardiograms, serum electrolytes, hepatic and renal function tests, and other laboratory studies also may be ordered. 

When two antiarrhythmic dragp are administered concurrently the patient may experience additive effects and is at increased risk for drug toxicity. When quinidine and procainamide are administered with digitalis, tiie risk of digitalis toxicity is increased. Hiarmacologic effects of procainamide may be increased when procainamide is administered with quinidine When quinidine is administered with the barbiturates or cimetidine, quinidine serum levels may be increased. When quinidine is administered with verapamil, there is an increased risk of hypotensive effects. When quinidine is administered with disopyramide, there is an increased risk of increased disopyramide blood levels and/or decreased serum quinidine levels. 

ADMINISTERING FLECAINIDE AND PROPAFENONE. When administering flecainide, die nurse must carefully monitor die patient for cardiac arrhythmias. Therapeutic serum levels fall between 0.2 and 1 pg/mL. Life support equipment, including pacemaker, should be kept on stand-by during administration. 

Fludrocortisone is contraindicated in patients with hypersensitivity to fludrocortisone and those with systemic fungal infections. Fludrocortisone is used cautiously in patients with Addison s disease infection, and during pregnancy (Pregnancy Category C) and lactation. Fludrocortisone decreases the effects of the barbiturates, hydantoins, and rifampin. There is a decrease in serum levels of the salicylates when those agents are administered with fludrocortisone... 

This is another group of diseases characterized by abnormalities in muscle fiber excitability. They are all periodic in the sense that periods of normal behavior are interspersed with periods of abnormally depressed excitability. During these latter phases, which may last for anything from a few hours to several days, there is a characteristic muscular weakness. The conditions are usually subdivided on the basis of serum levels during paralytic episodes, and are thus described as hyperkalemic, normokalemic, or hypokalemic. 

Maany I, Dhopesh V, Arndt lO, et al Increase in desipramine serum levels associated with methadone treatment. Am J Psychiatry 146 1611—1613, 1989 Maas U, Kattner E, Weingart-Jesse B, et al Infrequent neonatal opiate withdrawal following maternal methadone detoxification during pregnancy. J Perinat Med 18 111-118, 1990... 

The use of divalproex in benzodiazepine withdrawal has also become a common clinical strategy. It is usually started in doses of 500—1,000 mg in two or three divided doses daily and increased to achieve serum levels of 50—120 pg/mL. Some protocols recommend a loading dose of 20 mg/kg. 

An initial examination of the extent to which lithium may prevent cannabis withdrawal in rats was conducted by Cui et al. (2001), who reported that, at clinically relevant serum levels, lithium prevented the appearance of the cannabis withdrawal syndrome. The authors also noted that these effects were accompanied by a release of oxytocin, which they conclude is responsible for suppression of the withdrawal signs. 

There is limited information available regarding the distribution of methyl parathion after dermal exposure in humans. Two subjects, dermally exposed to methyl parathion, had 2.74 and 1.23 mg on their hands. Twenty-four hours after exposure, the serum levels were 0.027 and 0.032 mg/L, respectively (Ware et al. 1973). Twelve hours after cotton fields were sprayed, five men entered the treated fields for 5 hours. An average of 1.7 mg methyl parathion was detected on their hands. Serum concentrations averaged 0.156 mg/L in these subjects after 3 hours of exposure. Levels decreased to 0.1 and 0.002 mg/L at 2 and 24 hours postexposure, respectively (Ware et al. 1975). Although 0.5 mg methyl parathion was detected on the hands of four subjects, none was found in the serum (Ware et al. 1974). No information on the tissue distribution of methyl parathion in humans was found. 

Exposure of two species of freshwater fish to 0.106 ppb of a commercial formulation containing 50% methyl parathion increased serum levels of T3 and reduced T4 (Bhattacharya 1993). This effect was attributed to inhibition of acetylcholinesterase activity in the fish brain, but no direct evidence was presented. Similar treatment of freshwater perch for 35 days resulted in decreased release of progesterone from the ovaries (Bhattacharya and Mondal 1997). Also, treatment of freshwater perch for up to 90 days with methyl parathion induced a decrease in the gonadosomatic index (not defined) after day 15 of... 

The most specific biomarker of exposure to methyl parathion is the presence of the compound in serum or tissue. This is an especially good biomarker for detection shortly after acute exposure. For example, methyl parathion levels were detected in the sera of five men who were exposed for 5 hours in a cotton field 12 hours after it was sprayed with methyl parathion. The route of exposure was dermal, through unprotected hands. Serum levels averaged 156 ppb after 3 hours of the 5-hour exposure, and averaged 101.4 and 2.4 ppb at 7 and 24 hours postexposure, respectively (Ware et al. 1975). 

The chronic-duration oral MRL was derived based on the observation of increased serum levels of alkaline phosphatase (an indicator of hepatotoxicity) in dogs consuming 0.6 mg/kg/day for 1 year (Hoechst 1989c). The choice of this end point is supported by the observation of hydropic hepatic cells in rats that consumed 5 mg/kg/day for 2 years (EMC 1959b). The chronic-duration MRL of 0.002 mg/kg/day was derived by dividing the NOAEL for elevated serum alkaline phosphatase (0.18 mg/kg/day) by an uncertainty factor of 100 (10 for extrapolating from animals to humans, and 10 for human variability). 

Brock JW, Melynk LJ, Caudill SP, et al. 1998. Serum levels of several organochlorine pesticides in farmers correspond with dietary exposure and local use history. Toxicol Ind Health 14(l/2) 275-289. 

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