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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Pharmacy world & science 10 (1988), S. 185-188 
    ISSN: 1573-739X
    Keywords: Anticoagulants ; Blood coagulation ; Blood preservation ; Plasma ; Protein binding ; Serum ; Therapeutic drug monitoring ; Toxicology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The relative merits of plasma and serum in blood analysis are reviewed. The expression ‘plasma concentration’ is often used in the literature, although serum samples have been taken. In most cases serum and plasma concentrations of analytes are the same. The choice depends mostly on the policy of the hospital or the availability of the test tubes in the ward. Some of the advantages of plasma over serum are large volume, no delayed clotting, less risk of haemolysis. In addition, the sample is often suitable for both whole blood and plasma monitoring. Some of the disadvantages of plasma over serum are the (unknown) influence of the anticoagulant on the assay, on the protein binding and on the stability of the sample, the (unknown) influence of additives or impurities in the anticoagulants on the assay and on the concentration, the risk of the formation of small clots and dilution of the sample.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-739X
    Keywords: Chromatography, high pressure liquid ; Clearance ; Metabolism ; Nalidixic acid ; Pharmacokinetics ; Protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Nalidixic acid is metabolized by hydroxylation to 7-hydroxymethylnalidixic acid∥ and then by oxidation to 7-carboxynalidixic acid.∥ The half-lives of the two elimination phases of nalidixic acid are 0.75 and 2.5 h. The apparent half-lives of the metabolite 7-hydroxymethylnalidixic acid are 2.5 and 5.5 h. Plasma protein binding of nalidixic acid is 95% and that of 7-hydroxymethylnalidixic acid 65%. The renal clearance of nalidixic acid varies between 2 and 25 ml/min and that of 7-hydroxymethylnalidixic acid between 37 and 162 ml/min. Of nalidixic acid 42% is glucuronidated and 40% hydroxylated. Of the hydroxy metabolite 57% is glucuronidated and 32% excreted unchanged. 7-Carboxynalidixic acid is excreted in the urine and is not glucuronidated. The variations in the glucuronidation/ hydroxylation ratio of nalidixic acid and the glucuronidation/renal excretion ratio of the 7-hydroxymethyl metabolite belong to a normal distribution.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pharmacy world & science 10 (1988), S. 287-290 
    ISSN: 1573-739X
    Keywords: Benzodiazepines ; Drug concentration ; Nitrazepam ; Polymorphism ; Protein binding ; Saliva ; Serum ; Serum albumin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-739X
    Keywords: Chromatography, high pressure liquid ; Clearance ; Metabolism ; Pharmacokinetics ; Protein binding ; Sulfadimethoxine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Sulfadimethoxine is metabolized byO-dealkylation, N4-acetylation and N1-glucuronidation. In man, only N1-glucuronidation and N4-acetylation takes place, leading to the final double conjugate N4-acetylsulfadimethoxine-N1-glucuronide. The N1-glucuronides are directly measured by high pressure liquid chromatography. When N4-acetylsulfadimethoxine is administered as parent drug, 30% of the dose is N1-glucuronidated and excreted. Fast acetylators show a shorter half-life for sulfadimethoxine than slow acetylators (27.8±4.2 h versus 36.3±5.4 h; P=0.013), similarly the half-life of the N4-acetyl conjugate is also shorter in fast acetylators (41.3±5.2 h versus 53.5±8.5 h, P=0.036). No measurable plasma concentrations of the N1-glucuronides from sulfadimethoxine are found in plasma. N1-glucuronidation results in a 75% decrease in protein binding of sulfadimethoxine. N4-acetylsulfadimethoxine and its N1-glucuronide showed the same high protein binding of 99%. Approximately 50–60% of the oral dose of sulfadimethoxine is excreted in the urine, leaving 40–50% for excretion into bile and faeces.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Pharmacy world & science 8 (1986), S. 302-304 
    ISSN: 1573-739X
    Keywords: Blood specimen collection ; Carbamazepine ; Dialysis ; Digitoxin ; Lipolysis ; Protein binding ; Therapeutic drug monitoring ; Ultrafiltration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Pharmacy world & science 9 (1987), S. 50-55 
    ISSN: 1573-739X
    Keywords: Absorption ; Adult ; Aged ; Child ; Clearance ; Metabolism ; Pharmacokinetics ; Protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Age significantly affects therapeutics in both general and specific ways. In newborns and in infants various physiological processes are still developing, whereas in elderly there may be decreased efficiency or capacity of physiological processes. Unexpected or ‘idiosyncratic’ responses to drugs in the very old or in the very young often can be explained by age-related changes in absorption, distribution, metabolism, end-organ responsiveness and excretion. Adolescence is often associated with rapid growth and changing body composition. Special problems with adolescents are poor compliance and drug abuse. Adults show a rather stable pharmacokinetic profile, although the cardiac output diminishes and the peripheral resistance increases about 1% annually. Exposure to enzyme-inducing agents (nicotine, cimetidine) influences the pharmacokinetic parameters of both adolescents and adults.
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  • 7
    ISSN: 1573-739X
    Keywords: Albumins ; Digitoxin ; Hemodialysis ; Kidney diseases ; Orosomucoid ; Protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Plasma protein binding of most acidic drugs is decreased in uraemia, whereas the binding of basic drugs is usually unchanged or decreased. Decreased protein binding in patients with renal disease mainly relates to drugs binding to albumin. Digitoxin binds to a specific site on the albumin molecule. Conflicting reports exist on digitoxin-protein binding in patients with renal disease. In ten patients with end-stage renal disease treated with haemodialysis we found only a slightly increased free fraction of digitoxin. A heparin-induced increase of the free fraction of digitoxin during haemodialysis has been reported. However, this increase was caused by the generation of non-esterified fatty acidsin vitro. If thisin vitro lipolysis was blocked, no increase of free digitoxin could be detected. Alterations of digitoxin-protein binding in uraemic patients during haemodialysis and during the intervals between haemodialysis treatments are small.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Pharmacy world & science 9 (1987), S. 79-84 
    ISSN: 1573-739X
    Keywords: Clearance, hepatic ; Liver diseases ; Pharmacokinetics ; Protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Some general pharmacokinetic principles, relevant to understand and predict altered disposition of drugs in liver disease, are reviewed. It is appropriate to differentiate between high- and low-clearance drugs as to the influence of hepatic dysfunction. On intravenous administration highclearance drugs generally show reduced systemic clearance predominantly caused by decreased liver blood flow, whereas on oral administration a considerable increase in systemic availability may occur caused by reduced enzyme activity and (in cirrhosis) bij portacaval shunting. Low-clearance drugs are sensitive to reduced enzyme activity and reduced protein binding. It seems that oxidative reactions are far more affected than conjugation reactions in liver disease. Large inter-patient variability exists in the kinetics of a drug in any type of hepatic disease. The conventional liver-function tests are of no value in predicting altered drug disposition.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-739X
    Keywords: Cefoxitin ; Ceftazidime ; Ceftriaxone ; Cefuroxime ; Chromatography, high pressure liquid ; Kidney diseases ; Pharmacokinetics ; Protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A pharmacokinetic study after a single dose of ceftriaxone, cefoxitin, cefuroxime and ceftazidime was performed to investigate the influence of protein binding and severity of disease on the renal elimination. In intensive-care patients drug-protein binding was substantially less compared to that in volunteers and patients with less complicated diseases. This did not result in increased elimination but, due to increased apparent volumes of distribution, prolonged half-life times were observed. Consequently, in patients with complicated disease states a dosage regimen should be based on pharmacokinetic studies performed in a similar patient group.
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  • 10
    ISSN: 1573-739X
    Keywords: Administration, intraperitoneal ; Clearance ; Kidney diseases ; Peritoneal dialysis, continuous Ambulatory ; Peritonitis ; Pharmacokinetics ; Protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Transport of solutes across the peritoneal membrane in continuous ambulatory peritoneal dialysis (CAPD) is determined by patient-related factors (concentration gradient, membrane surface area, blood flow and membrane permeability) and by drug-related factors (charge on the molecule, protein binding, molecular weight, lipophilicity). On the basis of the chemical properties of a drug a prediction of the peritoneal clearance rate in CAPD patients is given, by the formulaCL capd = 75√free fraction/molecular weight. The implications of this formula are discussed. It is concluded that usually it is not necessary to change the dose as compared with end-stage renal disease patients who are not treated with CAPD.
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