Abstract：
OBJECTIVE:To determine the pharmacokinetics and organ distribution of i.v. and oral methylene blue, which is used to prevent ifosfamide-induced encephalopathy in oncology. METHODS:The concentration of methylene blue in whole blood was measured using high-performance liquid chromatography in seven volunteers after i.v. and oral administration of 100 mg methylene blue with and without mesna. The distribution of methylene blue in different tissues was measured in rats after intraduodenal and i.v. application. RESULTS:The time course of methylene blue in whole blood after i.v. administration showed a multiphasic time course with an estimated terminal half-life of 5.25 h. Following oral administration, the area under the concentration-time curve was much lower (9 nmol/min/ml vs 137 nmol/min/ml). Co-administration of mesna, which could influence distribution by ion-pairing, did not alter the pharmacokinetics. The urinary excretion of methylene blue and its leucoform was only moderately higher after i.v. administration (18% vs 28% dose). Intraduodenal administration to rats resulted in higher concentrations in intestinal wall and liver but lower concentrations in whole blood and brain than i.v. methylene blue. CONCLUSIONS:Differences in organ distribution of methylene blue are mainly responsible for the different pharmacokinetics after oral and i.v. administration. If methylene blue acts in the liver, where ifosfamide is primarily activated to reactive and potentially toxic metabolites, oral and i.v. methylene blue are likely to be equally effective. However, if the site of action is the central nervous system, i.v. methylene blue which results in much higher concentrations in brain seems preferable.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Peter C,Hongwan D,Küpfer A,Lauterburg BHdoi
10.1007/s002280000124subject
Has Abstractpub_date
2000-06-01 00:00:00pages
247-50issue
3eissn
0031-6970issn
1432-1041journal_volume
56pub_type
杂志文章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：:The pharmacokinetics of oral L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) was studied in 7 normal subjects and 7 patients with familial amyloid polyneuropathy. Each person swallowed a single 300 mg dose in the fasting state, and L-threo-DOPS in plasma and urine was determined by high performance liquid chromatogra...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00605999
更新日期：1982-01-01 00:00:00
abstract：PURPOSE:Fibroblast growth factor receptor 4 (FGFR4) expression has association with tumor malignancy. In thyroid cancers, FGFR4 has been reported to be characteristically expressed in aggressive thyroid tumors, such as anaplastic thyroid carcinoma (ATC). METHODS:We investigated FGFR4 expression in patients with ATC an...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-02842-y
更新日期：2020-05-01 00:00:00
abstract：:The purpose of the study was to examine long-term nicotine substitution and its variability during use of a nicotine patch. In two smoking cessation studies a 16-h nicotine patch, releasing 15 mg nicotine, was applied daily for 16 h over 12 weeks, to 167 smokers. Salivary cotinine was highly correlated with plasma cot...
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/BF02280755
更新日期：1992-01-01 00:00:00
abstract：:The pharmacokinetics and metabolism of quinidine were investigated in extensive and poor metabolisers of sparteine. No differences in plasma clearance, terminal half life, volume of distribution or cumulative urinary excretion of quinidine, 3-hydroxyquinidine and quinidine-N-oxide were observed between phenotypes. Thu...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00870989
更新日期：1986-01-01 00:00:00
abstract：:The most important cardiovascular interactions between cardioactive drugs and monoamino-oxidase inhibitors or tricyclic antidepressants are reviewed. Post-ganglion blocking agents (e.g., guanethidine), clonidine, reserpine, and alpha-methyl-dopa should not be used in patients needing antide-present therapy. For hypert...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/BF00566537
更新日期：1977-01-01 00:00:00
abstract：PURPOSE:The quality of drug therapy is an important issue for nursing homes. This study aimed to assess the prevalence of polypharmacy and potentially inappropriate medications (PIMs) in a large sample of nursing home residents by using the data recorded during the preparation of pill dispensers. METHODS:This is a cro...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-016-2193-z
更新日期：2017-05-01 00:00:00
abstract：OBJECTIVE:To study the effect of cisplatin on plasma concentrations and urinary excretion of carnitine in ten patients with different malignancies treated with chemotherapy. METHODS:Carnitine concentrations were determined using a radioenzymatic assay and other metabolites by routine methods of clinical chemistry. Ren...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s002280050504
更新日期：1998-09-01 00:00:00
abstract：PURPOSE:Treatment with statins requires close monitoring of serum creatine kinase (CK) levels to prevent myopathy, a common and potentially serious dose-dependent adverse effect of these drugs. We have investigated the correlation between elevated CK levels and polymorphisms in the genes encoding transporters involved ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-014-1661-6
更新日期：2014-05-01 00:00:00
abstract：:To evaluate the possible effect of quinidine on digoxin bioavailability, the steady state digoxin kinetics was examined with and without concomitant quinidine therapy, in 7 cardiac patients after simultaneous administration of oral digoxin and intravenous [3H]-digoxin. In the presence of quinidine, the absorption rate...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00613925
更新日期：1983-01-01 00:00:00
abstract：OBJECTIVES:The objective of this study was to describe determinants of current and subsequent benzodiazepine use in an elderly population, the Paquid cohort. METHODS:The study was conducted on a cohort of 2,792 community-dwelling subjects 65 years of age or more living in the Gironde department, southwestern France. B...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280100326
更新日期：2001-08-01 00:00:00
abstract：:In an open triple crossover study in 8 patients with essential hypertension, the possibility has been investigated of whether the blood pressure lowering effect of hydrochlorothiazide 50 mg once daily was attenuated by co-administration for 4 weeks of ibuprofen 400 mg t.i.d., diclofenac 25 mg t.i.d. or sulindac 200 mg...
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/BF00606629
更新日期：1987-01-01 00:00:00
abstract：:The role of mental stress in the development of hypertension and coronary heart disease remains uncertain. Its effects are likely to depend on an interaction of at least three factors: the nature of the stressor, its perception by the individual, and the individual's physiological susceptibility. This type of interact...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-01-01 00:00:00
abstract：PURPOSE:Gefitinib is one of the standard treatments for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor mutations. It has been reported that acid suppressants (AS) decrease the anti-tumor effect of gefitinib by reducing its solubility. AS is sometimes necessary in cancer patients; however, prev...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-03013-9
更新日期：2020-10-07 00:00:00
abstract：:Six women, 13 to 16 weeks pregnant, and 12 women at 38 to 40 weeks gestation, received oral oxazepam about 12 h before legal abortion, by hysterotomy in the former and before elective caesarean section in the latter group. The concentrations of free and conjugated oxazepam in maternal and fetal plasma were determined ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00625804
更新日期：1980-04-01 00:00:00
abstract：:Procainamide was given to 20 patients with normal renal function as an i.v. bolus of 500 mg followed by 1.0 or 1.5 g eight-hourly by mouth in the form of a slow release preparation (Durules). 97.6 +/- 27.1 (SD)% of the oral procainamide was absorbed, the absorption half life being 1.54 h. The elimination half life fol...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00560459
更新日期：1978-12-01 00:00:00
abstract：:Seven patients with acutely elevated diastolic blood pressure (DBP greater than or equal to 135 mmHg) were treated with repeated injections of diazoxide 1 mg/kg body weight i.v. at 10-min intervals. If the DBP was not reduced to 110 mmHg or less after 5 injections, a dose of 5 mg/kg was given. Serum diazoxide (total a...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00613809
更新日期：1983-01-01 00:00:00
abstract：:Serotonin (5-HT) stimulates prolactin release. In the present study the ability of dexfenfluramine to increase serum prolactin was used as an index of central 5-HT function after acute and chronic pretreatment of volunteers with fluoxetine. Following a single-blind, random design, on each experimental day each volunte...
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/BF00191908
更新日期：1994-01-01 00:00:00
abstract：:The pharmacokinetics of a new sustained-release preparation of theophylline (Dilatrane à Action Prolongée capsules filled with homogenous microgranules) has been after its studied administration to 7 healthy volunteers at 8 p.m. in order to achieve therapeutic levels at night and in the morning. In separate trials the...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542169
更新日期：1984-01-01 00:00:00
abstract：PURPOSE:Tolvaptan is a selective vasopressin V2 receptor antagonist that can be given orally once daily for treatment of clinically significant hypervolemic and euvolemic hyponatremia (US and Europe) or extracellular volume expansion despite taking other diuretics (Japan). In vitro studies indicated that tolvaptan was ...
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/s00228-011-1106-4
更新日期：2012-02-01 00:00:00
abstract：:Eight patients were given flunitrazepam 2 mg orally, once daily for 28 consecutive days. The time-course of the plasma concentration of unchanged flunitrazepam and its principal metabolites were studied in detail after the first and last doses. Additional blood samples were collected immediately before administration ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00561899
更新日期：1980-01-01 00:00:00
abstract：:The aim of this multicentre randomised double blind study was to compare the efficacy and safety of the 200-300 mg sustained release diltiazem formulation administered once daily (200-300 SR) with standard diltiazem (D) given three or four times daily to patients with stable angina. Patients aged 59 years, with a repr...
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/BF00193700
更新日期：1995-01-01 00:00:00
abstract：:Seventeen patients underwent tonsillectomy 55-120 min after receiving oral phenoxymethylpenicillin 12.5 mg/kg bodyweight. The penicillin concentration in serum and tonsillar tissue in each patient was determined by a microbial assay. In 9 patients with tonsillar hyperplasia, but with no prior history of tonsillitis, t...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00315423
更新日期：1990-01-01 00:00:00
abstract：PURPOSE:To investigate interindividual variability in response to pain treatment, we characterized postoperative patients for morphine metabolism and for COMT, OPRM1 and UGT2B7 polymorphisms. METHODS:A total of 109 patients treated with morphine were genotyped by DNA sequencing for 12 DNA polymorphisms of the COMT, OP...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-013-1523-7
更新日期：2013-09-01 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
更新日期：1983-01-01 00:00:00
abstract：:The kinetics of mefloquine were studied in 12 healthy Thai male and 12 healthy Thai female volunteers. Mefloquine (MQ) was administered either alone (750 mg orally) or in combination (MSP) with sulphadoxine (1.5 g) and pyrimethamine (75 mg) to each of 6 male and 6 female subjects. Plasma concentrations of MQ were meas...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542191
更新日期：1987-01-01 00:00:00
abstract：:Eighty patients recovering from major operations were investigated to evaluate the influence of naloxone on the analgesic and respiratory depressant properties of buprenorphine. They were randomly assigned to two groups to self-administer either buprenorphine (Group B) or a mixture of buprenorphine and naloxone (fract...
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/BF00542434
更新日期：1988-01-01 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:To investigate adherence to prescription in a female population aged 35-65 years. DESIGN:Postal questionnaire study of 2991 randomly sampled 35- to 64-year-old women in seven provinces of central Sweden. METHODS:The study was performed in 1995 as a cross-sectional postal questionnaire study in seven countie...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-006-0246-4
更新日期：2007-03-01 00:00:00
abstract：OBJECTIVE:To assess the pharmacokinetics, safety and tolerability of escalating oral doses of GW420867X, a non-nucleoside reverse transcriptase inhibitor, was investigated in healthy male volunteers in a randomized, double-blind placebo-controlled study. METHODS:Study subjects were divided into four groups of 12 subje...
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/s002280000224
更新日期：2001-01-01 00:00:00
