Abstract:
AIMS:To investigate uptake of fluconazole into the interstitial fluid of human subcutaneous tissue using the microdialysis and suction blister techniques. METHODS:A sterile microdialysis probe (CMA/60) was inserted subcutaneously into the upper arm of five healthy volunteers following an overnight fast. Blisters were induced on the lower arm using gentle suction prior to ingestion of a single oral dose of fluconazole (200 mg). Microdialysate, blister fluid and blood were sampled over 8 h. Fluconazole concentrations were determined in each sample using a validated HPLC assay. In vivo recovery of fluconazole from the microdialysis probe was determined in each subject by perfusing the probe with fluconazole solution at the end of the 8 h sampling period. Individual in vivo recovery was used to calculate fluconazole concentrations in subcutaneous interstitial fluid. A physiologically based pharmacokinetic (PBPK) model was used to predict fluconazole concentrations in human subcutaneous interstitial fluid. RESULTS:There was a lag-time (approximately 0.5 h) between detection of fluconazole in microdialysate compared with plasma in each subject. The in vivo recovery of fluconazole from the microdialysis probe ranged from 57.0 to 67.2%. The subcutaneous interstitial fluid concentrations obtained by microdialysis were very similar to the unbound concentrations of fluconazole in plasma with maximum concentration of 4.29 +/- 1.19 microg ml(-1) in subcutaneous interstitial fluid and 3.58 +/- 0.14 microg ml(-1) in plasma. Subcutaneous interstitial fluid-to-plasma partition coefficient (Kp) of fluconazole was 1.16 +/- 0.22 (95% CI 0.96, 1.35). By contrast, fluconazole concentrations in blister fluid were significantly lower (P < 0.05, paired t-test) than unbound plasma concentrations over the first 3 h and maximum concentrations in blister fluid had not been achieved at the end of the sampling period. There was good agreement between fluconazole concentrations derived from microdialysis sampling and those estimated using a blood flow-limited PBPK model. CONCLUSIONS:Microdialysis and suction blister techniques did not yield comparable results. It appears that microdialysis is a more appropriate technique for studying the rate of uptake of fluconazole into subcutaneous tissue. PBPK model simulation suggested that the distribution of fluconazole into subcutaneous interstitial fluid is dependent on tissue blood flow.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Sasongko L,Williams KM,Day RO,McLachlan AJdoi
10.1046/j.1365-2125.2003.01930.xkeywords:
subject
Has Abstractpub_date
2003-11-01 00:00:00pages
551-61issue
5eissn
0306-5251issn
1365-2125pii
1930journal_volume
56pub_type
杂志文章abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Nitrates may facilitate syncope through various pathways, but the precise mechanism of nitrate-induced syncope is still under debate. The purpose of the present study was to compare the underlying haemodynamic mechanisms in subjects without and with presyncopal symptoms during a...
journal_title:British journal of clinical pharmacology
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2000-05-01 00:00:00
abstract:AIMS:Establishing a pharmacological challenge model could yield an important tool to understand the complex role of the nicotinic cholinergic system in cognition and to develop novel compounds acting on the nicotinic acetylcholine receptor. METHODS:This randomized, double-blind, double-dummy, placebo-controlled, four-...
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pub_type: 杂志文章,随机对照试验
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abstract::1. Fifty-four depressive in-patients aged 18-45 yr, were treated at random, in double-blind conditions, with mianserin 60 mg daily or imipramine 150 mg daily in three divided doses for 4 weeks. Nitrazepam and diazepam were also allowed if necessary. 2. There was no significant difference in antidepressant efficacy bet...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
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abstract::1. The oral kinetics of oxazepam after a single 15 mg oral dose was investigated in six healthy volunteers before and during concomitant administration of the beta-adrenoceptor antagonists propranolol (80 mg) and labetalol (200 mg) (racemates). 2. A possible pharmacodynamic interaction between oxazepam and the beta-ad...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 临床试验,杂志文章
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doi:10.1111/j.1365-2125.1981.tb01327.x
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abstract::1. Compliance with digoxin therapy has been assessed in a group of fifty patients receiving the drug in general practice but not attending hospital. 2. Compliance was estimated by comparing plasma digoxin concentrations before and after a 10 day period of measured digoxin consumption and by tablet counting. 3. Twelve ...
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journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1991.tb05533.x
更新日期:1991-03-01 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1980-07-01 00:00:00
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abstract::1. To assess the risk of end-stage renal disease (ESRD) associated with the regular use of three classes of non-narcotic analgesics, we performed a case-control study of 340 patients with ESRD on a haemodialysis maintenance program and 673 hospital controls. 2. The overall odds ratio estimate for non-narcotic analgesi...
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pub_type: 临床试验,杂志文章,随机对照试验
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abstract::1 Herbal preparations containing atropine-like alkaloids are marketed as proprietory asthma remedies, typically in the form of cigarettes. 2 This randomised, cross-over study compares in six healthy volunteers the pharmacological effects caused by smoking a standard, medium tar, tobacco cigarette or a herbal cigarette...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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doi:10.1046/j.1365-2125.1996.03121.x
更新日期:1996-04-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb03821.x
更新日期:1990-10-01 00:00:00
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更新日期:1979-01-01 00:00:00
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更新日期:2009-09-01 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:2008-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2018-06-01 00:00:00