Abstract:
AIMS:Whereas cortical EEG effects of benzodiazepines are well characterized, information about benzodiazepine effects in other areas of the central nervous system is sparse. This study investigated the action of midazolam and its active metabolite alpha-hydroxy-midazolam on different parts of the auditory pathway in six healthy volunteers in a randomized, double-blind, three-way cross-over study. METHODS:Acoustically evoked short (SLP) and middle (MLP) latency potentials, transitory evoked otoacoustic emissions (TEOAE), and EEG power spectra were analysed after short i. v. injections of placebo, or 0.15 mg kg-1 midazolam, or alpha-hydroxy-midazolam, respectively. RESULTS:All subjects fell asleep during the 4 min infusion of active drug. SLP showed a significant transient increase of Jewett wave V 10 min after injection for midazolam and alpha-hydroxy-midazolam while the latency of wave I was unchanged. Both benzodiazepines induced a marked and long-lasting MLP amplitude decrease for 240 min with slow recovery over the following 360 min. No changes of TEOAE were observed. In agreement with earlier reports, increases in EEG beta activity and decreases in alpha activity were observed after administration of either drug. CONCLUSIONS:Systemically administered benzodiazepines modulate the auditory pathway above the level of the cochlea. While SLP changes were closely associated with sedation and high plasma benzodiazepine concentrations, MLP effects persisted for hours after sedation even at low benzodiazepine plasma levels. Evoked potentials may therefore be more sensitive than EEG as a tool to monitor benzodiazepine effects.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Hotz MA,Ritz R,Linder L,Scollo-Lavizzari G,Haefeli WEdoi
10.1046/j.1365-2125.2000.00104.xkeywords:
subject
Has Abstractpub_date
2000-01-01 00:00:00pages
72-9issue
1eissn
0306-5251issn
1365-2125pii
104journal_volume
49pub_type
临床试验,杂志文章,随机对照试验abstract::1. A survey has been conducted amongst 459 members of the Clinical Section of the British Pharmacological Society to ascertain facts about the administration of drugs to healthy volunteers over the period October 1986 to September 1987. 2. A response rate of 87.1% was obtained with 114 individuals being involved in he...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1989.tb05342.x
更新日期:1989-02-01 00:00:00
abstract:AIMS:To compare the lung delivery of salbutamol from a commonly used constant output open vent jet nebuliser (Sidestream) with use of both a conventional large volume plastic spacer (Volumatic) and a novel small volume metal spacer (NebuChamber). This was assessed using the early lung absorption profile of salbutamol o...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2125.1998.00648.x
更新日期:1998-02-01 00:00:00
abstract::The metabolism of [3H]ethinyloestradiol (EE2) was investigated in six male subjects who had been phenotyped with respect to sparteine metabolism (three metabolizers and three non-metabolizers). Urinary metabolite profiles of EE2 were virtually identical. Following enzyme hydrolysis of sulphate and glucuronide conjugat...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02511.x
更新日期:1984-10-01 00:00:00
abstract::Phenytoin drug reaction with eosinophilia and systemic symptoms (DRESS) in 3 Aboriginal Australians positive for HLA-B*56:02 has been previously reported. We report the allele frequency of HLA-B*56:02 in 2 South Australian populations, 1 Aboriginal (4.8%, 95% confidence interval 2.4-7.8%) and the other European (0%). ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14025
更新日期:2019-09-01 00:00:00
abstract:AIMS:Previously, we determined the phenotyping of in vivo nicotine metabolism and the genotyping of the CYP2A6 gene (CYP2A6*1 A, CYP2A6*1B, CYP2A6*2, CYP2A6*3, CYP2A6*4 and CYP2A6*5 ) in 92 Japanese and 209 Koreans. In the study, we found one Korean and four Japanese subjects genotyped as CYP2A6*1B/CYP2A6*4 who reveale...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2002.01667.x
更新日期:2002-11-01 00:00:00
abstract::1. The pharmacokinetics of streptokinase (SK) and anistreplase in conventional dosage regimens of 1.5 x 10(6) i.u. of SK infused over 60 min and 30 units of anistreplase over 5 min were studied in 24 consecutive patients presenting with acute myocardial infarction, using a functional bioassay to assess concentrations....
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1991.tb05502.x
更新日期:1991-02-01 00:00:00
abstract:AIM:Propylene glycol (PG) is often applied as an excipient in drug formulations. As these formulations may also be used in neonates, the aim of this study was to characterize the pharmacokinetics of propylene glycol, co-administered intravenously with paracetamol (800 mg PG/1000 mg paracetamol) or phenobarbital (700 mg...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2012.04312.x
更新日期:2013-01-01 00:00:00
abstract::1. The pharmacokinetics of didanosine, trimethoprim, and sulphamethoxazole were evaluated in ten HIV seropositive asymptomatic patients as single agents and upon coadministration of single doses. 2. Using a randomized, balanced incomplete block crossover study with at least a 1-week washout period between successive t...
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.1365-2125.1996.tb00184.x
更新日期:1996-03-01 00:00:00
abstract::Although blood pressure measured at the brachial artery plays a central role in our understanding and management of cardiovascular risk, in recent years great emphasis has been placed on the importance of central blood pressure. It seems straightforward that knowledge of the blood pressure directly affecting the major...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2012.04203.x
更新日期:2012-08-01 00:00:00
abstract:AIM:To examine comprehensively the relationship between exposure to four classes of psychotropic drugs including antipsychotics, antidepressants, benzodiazepines (BZDs) and Z-drugs, and motor vehicle accidents (MVAs). METHOD:The authors conducted a matched case-control study of 5183 subjects with MVAs and 31 093 match...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2012.04410.x
更新日期:2013-04-01 00:00:00
abstract:AIM:To assess the effect of Schisandra sphenanthera extract (SchE) on the pharmacokinetics of tacrolimus in healthy volunteers. METHODS:Twelve healthy male volunteers were orally treated with SchE, three capsules twice daily for 13 days. Pharmacokinetic investigations of oral tacrolimus administration at 2 mg were per...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2007.02922.x
更新日期:2007-10-01 00:00:00
abstract:AIMS:There is a trend for more flexibility in timing of evidence generation in relation to marketing authorization, including the option to complete phase III trials after authorization or not at all. This paper investigated the relation between phase II and III clinical trial efficacy in oncology. METHODS:All oncolog...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14237
更新日期:2020-07-01 00:00:00
abstract::1 Aspirin is partly hydrolyzed to salicylic acid during absorption. Absorbed aspirin is rapidly hydrolyzed systemically. Salicylic acid elimination kinetics are dependent on drug concentration due to the limited capacity of two major biotransformation pathways: formation of salicyluric acid and of salicylphenolic gluc...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1980.tb01811.x
更新日期:1980-10-01 00:00:00
abstract::Infections due to resistant and multidrug resistant (MDR) organisms in haematology patients and haematopoietic stem cell transplant recipients are an increasingly complex problem of global concern. We outline the burden of illness and epidemiology of resistant organisms such as gram-negative pathogens, vancomycin-resi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12310
更新日期:2015-02-01 00:00:00
abstract:AIMS:6-mercaptopurine (6-MP) is used in the treatment of childhood acute lymphoblastic leukaemia (ALL). Its red blood cell (RBC) metabolite concentrations (6-thioguanine [6-TGN] and 6-methylmercaptopurine nucleotides [6-MMPN]) are related to drug response. We investigated the impact of non-genetic covariates and pharma...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2010.03867.x
更新日期:2011-04-01 00:00:00
abstract::1. The localisation and distribution of cytochrome P-450 in human tissues has been studied by immunocytochemistry using a monoclonal antibody to a major form of human hepatic cytochrome P-450, P-450hA7, which is closely related to cytochromes P-450 HLp and P-450NF. 2. Strong immunoreactivity was identified in hepatocy...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb03331.x
更新日期:1988-04-01 00:00:00
abstract:AIMS:Korean red ginseng (unskinned Panax ginseng before it is steamed or otherwise heated and subsequently dried) is one of the most widely used herbal remedies. This systematic review evaluates the current evidence for the effectiveness of red ginseng for treating erectile dysfunction. METHODS:Systematic searches wer...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1111/j.1365-2125.2008.03236.x
更新日期:2008-10-01 00:00:00
abstract::1. The effect of icatibant (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8] bradykinin) a potent B2-kinin receptor antagonist, was studied on bradykinin-induced vasodilation in the human forearm. 2. Eight healthy normotensive men were studied in a rising dose random-placebo controlled study. Placebo and icatibant (20, 50 and 100 mic...
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.1365-2125.1994.tb04360.x
更新日期:1994-10-01 00:00:00
abstract::Serum and milk concentrations of aztreonam were studied in 12 lactating, healthy subjects over the 8 h period after the administration of a single intramuscular or intravenous 1 g dose. Milk concentrations of aztreonam were found to be much lower than serum concentrations at all time points after both routes of inject...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb02677.x
更新日期:1985-04-01 00:00:00
abstract::1 The effect of low dose steady state warfarin (0.2 mg and 1 mg daily) on clotting factor activity and vitamin K1 metabolism was studied in seven healthy volunteers. 2 Steady state plasma warfarin concentrations were 41-99 ng ml-1 for the 0.2 mg dose and 157-292 ng ml-1 for the 1 mg dose. 3 There was a significant pro...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb03274.x
更新日期:1988-01-01 00:00:00
abstract::1. A questionnaire examining the use of, and knowledge about over-the-counter (OTC) drugs was administered verbally to representatives from 200 urban and 200 rural households. Self-medication was common in both groups but there were more drugs present in rural (336 items) than urban homes (231 items) with the differen...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1989.tb03435.x
更新日期:1989-06-01 00:00:00
abstract::The airway and cardiovascular effects of intravenous neurokinin A (NKA) and substance P (SP) were compared in six normal subjects. Both SP and NKA increased skin temperature (SkT) and heart rate (HR), but SP was more potent than NKA by factors of 6 and 20 respectively. No change in systolic blood pressure (BP) occurre...
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.1365-2125.1988.tb03302.x
更新日期:1988-02-01 00:00:00
abstract:AIM:Drug-induced liver injury (DILI) is often responsible for acute liver failure, drug withdrawal, boxed warnings or drug non-approval. Therefore, we conducted a case-control study to determine the hepatotoxic risk of a wide range of drugs. METHODS:The Berlin Case-Control Surveillance Study FAKOS included all 51 Berl...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12565
更新日期:2015-06-01 00:00:00
abstract:AIMS:To explore the feasibility of delivering community-based drug safety testing (drug checking), to trial service design characteristics and to compare with festival-based testing. METHODS:In total, 171 substances of concern were submitted on 5 dates at 3 venues in 2 UK cities and tested using up to 6 analytical tec...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14231
更新日期:2020-03-01 00:00:00
abstract::Plasma and synovial fluid concentrations of the enantiomers of flurbiprofen were measured in 15 rheumatoid patients receiving 100 mg racemic flurbiprofen twice daily. Pharmacokinetic parameters showed considerable variability within the group of patients, although differences in S(+)/R(-) plasma concentration ratios w...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1991.tb03865.x
更新日期:1991-01-01 00:00:00
abstract::Mirabegron is used for the treatment of symptoms associated with overactive bladder syndrome. It selectively stimulates the β3 -adrenoreceptor, which relaxes the detrusor muscle. This improves urine storage by distension of the bladder body. ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12647
更新日期:2015-10-01 00:00:00
abstract::1. The attitudes of general practitioners and hospital physicians to the management of hypertension in the elderly, were examined by responses to a postal questionnaire distributed within the Northern Region, concerning the management of a healthy 75 year old male non-smoker with sustained diastolic or isolated systol...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1995.tb04481.x
更新日期:1995-05-01 00:00:00
abstract:AIMS:Angiotensin receptor blockers (ARBs) are renoprotective and targeted to blood pressure. However, ARBs have multiple other (off-target) effects which may affect renal outcome. It is unknown whether on-target and off-target effects are congruent within individuals. If not, this variation in short term effects may ha...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.12655
更新日期:2015-10-01 00:00:00
abstract::The pharmacokinetics of CGP 15 210 G, a new 5-HT uptake inhibitor in poor and extensive metabolisers of debrisoquine, give indirect evidence of an association between its metabolism and polymorphic hydroxylation of the debrisoquine type. ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb02802.x
更新日期:1985-07-01 00:00:00
abstract:AIMS:To ascertain the effects of the Medicines and Healthcare products Regulatory Agency's (MHRA) safety update in June 2010 on the volume of prescribing of quinine and on indices of quinine toxicity. METHODS:We analysed quarterly primary care total and quinine prescribing data for England and quinine prescribing volu...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12130
更新日期:2013-12-01 00:00:00