Abstract:
OBJECTIVE/METHODS:The metabolism of chloramphenicol succinate (CAPS) by human bone marrow was studied in vitro using 75 marrow samples. Whole marrow samples were incubated with CAPS with or without reduced nicotinamide adenine dinucleotide phosphate for 1, 2 and 3 h at 37 degrees C. Ficoll-paque-separated marrow mononuclear cells and erythrocytes were similarly incubated. After precipitation and centrifugation, clear supernatant was analysed for the presence of metabolites using high-performance liquid chromatography. RESULTS:Only one metabolite was detected when CAPS was incubated for 3 h with whole marrow from 72 donors. Its retention time (RT 10.9 min) corresponded to chloramphenicol (CAP). When CAPS was incubated with samples of whole marrow, marrow mononuclear cells, marrow erythrocytes, marrow plasma and peripheral blood from one donor who had taken Traditional Chinese Medicine (TCM), three metabolite peaks were detected within 15 min to 1 h. The RT of two of these peaks corresponded to CAP and nitroso-CAP (RT 14.9 min), but one peak remained unidentified. These peaks were not detected in the control samples incubated without CAPS. Blood samples collected after 3 months and 6 months to reconfirm metabolic activity yielded no such metabolite peaks when incubated with CAPS for 1-3 h. Therefore induction of enzyme activity by TCM was suspected. Three metabolite peaks with the same RTs were also detected when CAPS was incubated for 3 h with whole marrow from two other donors. CONCLUSION:These studies demonstrated that CAPS may be metabolised to CAP and occasionally other metabolites in human bone marrow. This novel observation is particularly important because the bone marrow is known to be a target organ for chloramphenicol toxicity.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Ambekar CS,Cheung B,Lee J,Chan LC,Liang R,Kumana CRdoi
10.1007/s002280000143subject
Has Abstractpub_date
2000-08-01 00:00:00pages
405-9issue
5eissn
0031-6970issn
1432-1041journal_volume
56pub_type
杂志文章abstract::We have shown that apparent nonlinearities in the pharmacokinetics of chloroquine and wide variability in reported kinetic values are possibly artefacts of experimental design. We have used simulated data based on linear equations to demonstrate that chloroquine kinetics may appear to be dose-dependent if samples are ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00541305
更新日期:1987-01-01 00:00:00
abstract::In a model of mental stress the influence of nifedipine and hydrochlorothiazide on stress-induced changes in blood pressure, heart rate, and plasma catecholamines was studied in normal persons. The drugs were used to investigate whether substances with antihypertensive but no particular sympatholytic properties were c...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00544008
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abstract::In the 3rd paragraph and 2nd line of the Conclusion section the correct sentence should be: It is now important to encourage policy and decision makers to facilitate and accommodate future linkage of data. ...
journal_title:European journal of clinical pharmacology
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abstract::Interaction of the main metabolites of diazepam and chlordiazepoxide with alcohol was measured in two subacute double-blind cross-over experiments on 40 healthy, young volunteers. The drugs were administered for two week periods. The variables measured were choice reaction time and accuracy, eye-hand co-ordination, di...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00644607
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abstract::The biliary excretion of mebendazole has been investigated in two patients to whom it was given for the treatment of echinococcosis, although it was found to be only partly effective. Oral mebendazole was extensively metabolized and the conjugated parent substance and its metabolites were excreted in the bile. One pat...
journal_title:European journal of clinical pharmacology
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abstract::The clearance of chlordiazepoxide from the systemic circulation was studied in 20 subjects which included 15 patients with alcoholic hepatitis and 5 normal volunteers. The half-life for the appearance of the drug in the systemic circulation was found to increase exponentially with age (r = 0.73, P less than 0.0005) an...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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abstract:OBJECTIVE:To investigate the usefulness of the 3-hydroxylation of quinine as a biomarker reaction for the activity of CYP3A4 in man and to study the interindividual variation in the metabolic ratio (MR), i.e. quinine/3-hydroxyquinine. METHODS:Data from a previous study (A) was used for determination of the MR of quini...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s00228-003-0621-3
更新日期:2003-08-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s00228-012-1307-5
更新日期:2013-01-01 00:00:00
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abstract:PURPOSE:To investigate possible differences in the time course of vasodilating effects of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in humans. METHODS:We measured forearm blood flow (FBF) by strain gauge plethymography and cyclic GMP spillover during and after intra-arterial infusions of BNP...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-008-0516-4
更新日期:2008-09-01 00:00:00
abstract::General well-being, adverse effects and anti-hypertensive efficacy have been investigated in a double blind, parallel-group, dose-response multicentre study of diltiazem and metoprolol monotherapy for hypertension. 128 patients with primary hypertension were included from 10 participating centres. The patients were ra...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/BF00315222
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:Ilaprazole, the latest proton pump inhibitor, can be used with clarithromycin and amoxicillin as a triple therapy regimen for eradicating Helicobacter pylori. The aim of this study was to evaluate pharmacokinetic drug interactions and safety profiles after coadministration of clarithromycin, amoxicillin, and il...
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更新日期:2018-09-01 00:00:00
abstract::The effects of short-term lithium (Li) administration on alpha 2-adrenoceptor sensitivity was studied in 10 healthy volunteers and in 15 patients with normothymic, phasic depressive disorders. The GH-clonidine test was used to examine alpha 2-adrenoceptor sensitivity, administered before and after Li treatment (600 mg...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00637595
更新日期:1988-01-01 00:00:00
abstract::The cellular sources or molecular mechanisms responsible for the derangement of vasoactive prostanoid levels during immunosuppressive cyclosporin (CSA) therapy have not been defined. Using cultured rat glomerular mesangial cells (MC), the cytostatic, cytotoxic and prostanoid synthesis modulating effects of CSA and FK-...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF01428385
更新日期:1993-01-01 00:00:00
abstract::1. The effect of pre-dosing with 15 mg domperidone, a relatively selective dopamine 2-receptor antagonist, on the ocular hypotensive action of a single oral dose of 25 micrograms pergolide, a dopamine 2-receptor agonist, was studied in 9 normal human volunteers, using a non-invasive method. 2. Compared with domperidon...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF02336684
更新日期:1990-01-01 00:00:00
abstract::The immediate haemodynamic and metabolic effects of acute dose of diazoxide 300 mg i.v. were studied in six healthy subjects at rest and during dynamic forearm exercise. Control periods of rest, exercise and recovery were compared with corresponding periods after drug administration. Resting forearm blood flow was alm...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542454
更新日期:1982-01-01 00:00:00
abstract:OBJECTIVE:Gentamicin population pharmacokinetics in newborns were studied with special reference to possible gender effects. METHODS:Steady-state serum levels ( n=139) were obtained from 79 neonates with a mean birth weight of 2.1 kg, mean gestational age of 35.1 weeks and mean age at the time of sampling of 4.2 days....
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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更新日期:2005-07-01 00:00:00
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journal_title:European journal of clinical pharmacology
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abstract:PURPOSE:To investigate if the ordinary use of a vaginal suppository containing miconazole results in systemic absorption that is sufficient to affect the activities of CYP1A2 and CYP3A4, which are major drug- and steroid-metabolising enzymes. METHODS:In 20 healthy non-pregnant women aged 18-45 years, the serum concent...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-010-0906-2
更新日期:2010-12-01 00:00:00
abstract::Repeated doses of a 1,5 benzodiazepine, clobazam, were administered to a group of consenting volunteers. Performance on a psychomotor performance task was not impaired by repeated doses of the drug. Subjective assessments of anxiety were reduced commensurate with an increase in the level of cortical integration, measu...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00644961
更新日期:1979-08-01 00:00:00
abstract:PURPOSE:The purpose of this study is to investigate the association between polypharmacy with health-related quality of life (HRQoL) and medication regimen complexity with HRQoL in residential aged care facilities (RACFs). METHODS:A cross-sectional study of 383 residents from six Australian RACFs was conducted. The pr...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-016-2075-4
更新日期:2016-09-01 00:00:00
abstract::A new technique which combines skin microinjection of minute amounts of drugs (0.5 microliter) and measurement of capillary permeability by intravital fluorescence videomicroscopy and densitometry is introduced. Glass micropipettes with a tip diameter of 7-9 microns are inserted by a micromanipulator into the stratum ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00203779
更新日期:1996-01-01 00:00:00
abstract::Drug binding in the interstitial fluid as well as in the plasma must be taken into account when considering the pharmacokinetics of drugs which are highly bound to plasma proteins and have a relatively small apparent volume of distribution (V). The half-life and apparent volume of distribution of such a drug can be af...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00609592
更新日期:1981-01-01 00:00:00
abstract:OBJECTIVE:The aim of this investigation was to determine whether mefenamic acid and salicylic acid inhibit the sulfation of (-)-salbutamol and minoxidil in the human liver and duodenum, and if so, to ascertain whether the 50% inhibitory concentration (IC50) estimates are different in the two tissues. METHODS:Sulfotran...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:2000-09-01 00:00:00
abstract::Plasma levels of canrenone and 'total metabolites' after base hydrolysis were compared in young and elderly subjects following single and multiple doses of spironolactone. After the initial dose on Day 1, plasma levels of canrenone and 'total metabolites' were higher in the young than in the elderly group, and signifi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00549591
更新日期:1984-01-01 00:00:00
abstract:PURPOSE:The 388A>G and the 521T>C polymorphism of the SLCO1B1 gene affect the activity of the uptake transporter OATP1B1, thus influencing kinetics, safety, and efficacy of substrate drugs. To evaluate the impact of these polymorphisms in populations of different ethnic origins, it is important to know their frequencie...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-011-1065-9
更新日期:2011-11-01 00:00:00
abstract::An expert meeting to discuss population pharmacokinetic/pharmacodynamic software was held in Brussels in November 1993 under the auspices of the European Co-operation in Science and Technology (COST), Medicine (B1) programme. Recently developed statistical methods offer the possibility of gaining integrated informatio...
journal_title:European journal of clinical pharmacology
pub_type:
doi:10.1007/BF00191898
更新日期:1994-01-01 00:00:00
abstract:OBJECTIVE:We investigated the frequencies of the functionally important variants of the CYP2A6 gene in black African populations. METHODS:Using genomic DNA sequencing, polymerase chain reaction (PCR)-restriction fragment length polymorphism and allele-specific PCR, the allele frequencies of CYP2A6 *1A, *1B, *2, *4A, *...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-004-0854-9
更新日期:2005-02-01 00:00:00