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1. |
Clinical Pharmacokinetics of Oxazepam and Lorazepam |
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Clinical Pharmacokinetics,
Volume 6,
Issue 2,
1981,
Page 89-105
David J. Greenblatt,
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摘要:
Oxazepam and lorazepam are 3-hydroxy benzodiazepine derivatives used as sedatives and anxiolytics. The major metabolic pathway for both compounds involves conjugation to glucuronic acid at the 3-position, followed by urinary excretion of the inactive glucuronide metabolite.Oxazepam has been administered to humans by the oral route only. Usual ranges for kinetic parameters are: elimination half-life, 5 to 15 hours; volume of distribution, 0.6 to 2.0L/kg; clearance, 0.9 to 2.0ml/min/kg. Age and liver disease have a minimal influence on oxazepam kinetics, but renal disease is associated with a prolonged half-life and increased volume of distribution.Typical kinetic values for lorazepam are: elimination half-life, 8 to 25 hours; volume of distribution, 1.0 to 1.3L/kg; clearance, 0.7 to 1.2ml/min/kg. Lorazepam clearance is somewhat reduced in old age, but liver disease has a minimal effect on clearance. Oral and intramuscular lorazepam are rapidly absorbed, with systemic availability averaging 90% or more.Both oxazepam and lorazepam are extensively bound to plasma protein, but the free fraction for lorazepam (8 to 12%) is greater than that for oxazepam (2 to 4%).
ISSN:0312-5963
出版商:ADIS
年代:1981
数据来源: ADIS
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2. |
Quality Control of Drug Assays |
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Clinical Pharmacokinetics,
Volume 6,
Issue 2,
1981,
Page 106-117
G. Ayers,
D. Burnett,
A. Griffiths,
A. Richens,
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摘要:
Previously published work relating to quality control of drug assays has dealt mainly with interlaboratory comparisons. It is suggested that participants in external quality assessment schemes will derive the maximum benefit from their participation if a suitable intralaboratory quality control scheme is established. Such a scheme should be capable of providing estimates of within- and between-batch imprecision over the concentration range for which the assay is used and give an indication of the development of systematic error (relative to previous performance). A scheme using serum pools at 3 concentrations, each to be analysed at least in duplicate, is recommended. Adaptations of this scheme, to be used when the number of patient samples per batch does not justify this number of control samples, are discussed in relation to various analytical situations. A ratio of 1 control sample to 10 patient samples is considered reasonable.The interpretation of results from external quality assessment schemes using performance indices, graphical assessment of ‘bias’ and standard deviation interval (SDI = bias divided by standard deviation) and the statistical evaluation of proportional and additive error by linear regression (least squares) analysis is discussed. In some cases it has been possible, from the results of interlaboratory studies, to show that a particular method will not generally give satisfactory results when compared either with other currently available methods, e.g. UV-spectrophotometric methods for phenobarbitone, phenytoin, carbamazepine and theophylline, or on the grounds of clinical requirements, e.g. doubling dilution broth techniques for gentamicin.Improvement in intralaboratory reproducibility would facilitate the identification of technical factors contributing to interlaboratory variation.
ISSN:0312-5963
出版商:ADIS
年代:1981
数据来源: ADIS
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3. |
Acetylator Phenotype and Lupus Erythematosus |
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Clinical Pharmacokinetics,
Volume 6,
Issue 2,
1981,
Page 118-134
Jack P. Uetrecht,
Raymond L. Woosley,
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摘要:
There are several known therapeutic implications of acetylator phenotype; among them, the association of a higher incidence of procainamide- and hydralazine-induced lupus in slow acetylators. Presumably, this is because acetylation of the aromatic amine or hydrazine functional group leads to a non-toxic product. Several other drugs which have been implicated in drug-induced lupus also contain an aromatic amine or hydrazine group.The clinical and laboratory characteristics of drug-induced and idiopathic lupus are similar but the degree to which the pathophysiological mechanisms are related, if at all, is unknown.There is also evidence reported for an association between the slow acetylator phenotype and idiopathic lupus. If true, this relationship should provoke some new experimental approaches to investigation into the mechanism of idiopathic lupus.
ISSN:0312-5963
出版商:ADIS
年代:1981
数据来源: ADIS
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4. |
Clinical Pharmacokinetics of Probenecid |
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Clinical Pharmacokinetics,
Volume 6,
Issue 2,
1981,
Page 135-151
R. F. Cunningham,
Z. H. Israili,
P. G. Dayton,
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摘要:
A review of the clinical applications and of the disposition of probenecid in man, including drug interactions, is presented.Probenecid is the classical competitive inhibitor of organic acid transport in the kidney and other organs. There are 2 primary clinical uses for probenecid: as a uricosuric agent in the treatment of chronic gout and as an adjunct to enhance blood levels of antibiotics (such as penicillins and cephalosporins). Adsorption of probenecid is essentially complete following oral administration. The drug is extensively metabolised by glucuronide conjugation and by oxidation of the alkyl side chains; oxidation of the aromatic ring does not occur. The half-life of probenecid in plasma (4 to 12 hours) is dose-dependent. Renal excretion is the major route of elimination of the metabolites; excretion of the parent drug is minimal and is dependent on urinary pH. Probenecid and its oxidised metabolites are extensively bound to plasma proteins, mainly to albumin. Tissue concentrations (based on animal studies) are generally lower than plasma concentrations.Most of the drug-drug interactions involving probenecid are due to an effect on the kidneyblock of transport of acidic drugs. Similarly probenecid affects the tubular secretion of a number of acidic endogenous substances by the kidney. Probenecid is also involved in the block of transport of acidic metabolites of catecholamines, for example homovanillic and hydroxyindoleacetic acids, in the brain. There are a number of analytical procedures for the assay of probenecid. These are based on spectrophotometry, spectrofluorometry, gas and liquid chromatography and radioimmunoassay.
ISSN:0312-5963
出版商:ADIS
年代:1981
数据来源: ADIS
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5. |
The Effect of Malnutrition on the Pharmacokinetics of Phenylbutazone |
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Clinical Pharmacokinetics,
Volume 6,
Issue 2,
1981,
Page 152-159
K. Krishnaswamy,
V. Ushasri,
A. Nadamuni Naidu,
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摘要:
The pharmacokinetics of phenylbutazone were studied after a single oral dose of 6mg/kg bodyweight in 35 adult male subjects with differing nutritional status.The elimination half-life was significantly shorter and plasma clearance accelerated in undernourished patients who had significant weight deficit and low serum albumin concentration. Plasma protein binding was only 86% compared with 95 to 96% in normal subjects (smokers and non-smokers). The apparent volume of distribution was also higher in undernourished patients. Significant correlations were observed between serum albumin, protein binding and bodyweight.Multiple regression analysis of the data indicated that altered drug protein binding partially contributed towards variation in half-life and clearance; and the plasma albumin concentration significantly influenced the amount of drug bound in plasma.The results indicate that nutritional status is one of the important environmental variables that can alter drug kinetics and disposition in man. Further studies, including measurement of steady-state plasma concentrations of various other drugs, are necessary to elucidate drug kinetics in malnourished subjects.
ISSN:0312-5963
出版商:ADIS
年代:1981
数据来源: ADIS
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6. |
Current Literature References on Clinical Pharmacokinetics |
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Clinical Pharmacokinetics,
Volume 6,
Issue 2,
1981,
Page 160-160
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PDF (79KB)
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ISSN:0312-5963
出版商:ADIS
年代:1981
数据来源: ADIS
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