Abstract：
AIM:We aimed to establish a method to assess systemic and pre-systemic cytochrome P450 (CYP) 3A activity using ineffective microgram doses of midazolam. METHODS:In an open, one sequence, crossover study, 16 healthy participants received intravenous and oral midazolam at microgram (0.001 mg intravenous and 0.003 mg oral) and regular milligram (1 mg intravenous and 3 mg oral) doses to assess the linearity of plasma and urine pharmacokinetics. RESULTS:Dose-normalized AUC and Cmax were 37.1 ng ml(-1 ) h [95% CI 35.5, 40.6] and 39.1 ng ml(-1) [95% CI 30.4, 50.2] for the microdose and 39.0 ng ml(-1 ) h [95% CI 36.1, 42.1] and 37.1 ng ml(-1) [95% CI 26.9, 51.3] for the milligram dose. CLmet was 253 ml min(-1) [95% CI 201, 318] vs. 278 ml min(-1) [95% CI 248, 311] for intravenous doses and 1880 ml min(-1) [95% CI 1590, 2230] vs. 2050 ml min(-1) [95% CI 1720, 2450] for oral doses. Oral bioavailability of a midazolam microdose was 23.4% [95% CI 20.0, 27.3] vs. 20.9% [95% CI 17.1, 25.5] after the regular dose. Hepatic and gut extraction ratios for microgram doses were 0.44 [95% CI 0.39, 0.49] and 0.53 [95% CI 0.45, 0.63] and compared well with those for milligram doses (0.43 [95% CI 0.37, 0.49] and 0.61 [95% CI 0.53, 0.70]). CONCLUSION:The pharmacokinetics of an intravenous midazolam microdose is linear to the applied regular doses and can be used to assess safely systemic CYP3A activity and, in combination with oral microdoses, pre-systemic CYP3A activity.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Hohmann N,Kocheise F,Carls A,Burhenne J,Haefeli WE,Mikus Gdoi
10.1111/bcp.12502subject
Has Abstractpub_date
2015-02-01 00:00:00pages
278-85issue
2eissn
0306-5251issn
1365-2125journal_volume
79pub_type
杂志文章abstract：:The discovery of immune checkpoints and their role in modulating immune response have revolutionised cancer treatment in recent years. The immune checkpoints, cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1 and its ligand, programmed cell death-ligand 1, have been extensively studied. Curr...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.14338
更新日期：2020-09-01 00:00:00
abstract：:Systemic cardiovascular effects during chronic treatment with topical minoxidil vs placebo were evaluated using a double-blind, randomized design for two parallel groups (n = 20 for minoxidil, n = 15 for placebo). During 6 months of follow-up, blood pressure did not change, whereas minoxidil increased heart rate by 3-...
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.tb03410.x
更新日期：1988-10-01 00:00:00
abstract：:1. We present a novel index for expressing the exposure of the infant to drugs in breast milk, which unifies two independent factors: a pharmacokinetic parameter, drug clearance, and a physiochemical parameter, i.e. milk-to-maternal plasma drug concentration ratio (M/P ratio). 2. During breast-feeding by a woman recei...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1994.tb04331.x
更新日期：1994-08-01 00:00:00
abstract：AIMS:Endothelins (ETs) may play a role in the pathogenesis of a variety of cardiovascular diseases. The present study was designed to investigate the pharmacokinetic and pharmacodynamic effects of the orally active ETA selective receptor antagonist ABT-627 in healthy humans. METHODS:Healthy volunteers were included in...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1046/j.1365-2125.2000.00171.x
更新日期：2000-06-01 00:00:00
abstract：WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:* Exposure to bosentan was lower in paediatric pulmonary arterial hypertension (PAH) patients treated with the marketed adult formulation at a dose of about 2 mg kg(-1) when compared with adult PAH patients. * In healthy adult subjects, bosentan pharmacokinetics are less than do...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1111/j.1365-2125.2009.03532.x
更新日期：2009-12-01 00:00:00
abstract：AIMS:Helicobacter pylori (H. pylori) eradication rate varies according to the treatment regimen used and other factors, e.g. antimicrobial resistance and patient compliance. The aim of the present study was to evaluate the influence of patient counselling and follow-up on H. pylori eradication rates and to document the...
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.0306-5251.2001.01531.x
更新日期：2002-02-01 00:00:00
abstract：:1. Six healthy volunteers received single doses of either nomifensine 100 mg, nomifensine 50 mg or placebo at weekly intervals in a randomized double-blind crossover study. 2. Subjects were subjected to a simulated test of car driving at night. 3. Testing lasted about 1.5 h and consisted of measuring responses to ligh...
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.1365-2125.1977.tb05748.x
更新日期：1977-01-01 00:00:00
abstract：:The in vitro conversion of enalapril (MK421) to enalaprilic acid (MK422) in human autopsy tissues was examined. MK422 was measured by radioimmunoassay. Human cadaver liver was the only tissue in which significant conversion was demonstrated. The esterase activity was stable after post mortem. Autopsy liver tissues fro...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1985.tb02699.x
更新日期：1985-05-01 00:00:00
abstract：AIMS:Grapefruit juice inhibits CYP3A4 in the intestinal wall leading to a reduced intestinal first pass metabolism and thereby an increased oral bioavailability of certain drugs. For example, it has been shown that the oral bioavailability of midazolam, a CYP3A4 substrate, increased by 52% in healthy subjects after ing...
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.1365-2125.2002.01615.x
更新日期：2002-08-01 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：AIMS:Drug disposition in children may vary from adults due to age-related variation in drug metabolism. Microdose studies present an innovation to study pharmacokinetics (PK) in paediatrics; however, they should be used only when the PK is dose linear. We aimed to assess dose linearity of a [14 C]midazolam microdose, b...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1111/bcp.14047
更新日期：2019-10-01 00:00:00
abstract：:1 The effects of age and sex on the disposition of clobazam (CBZ), a 1.5-benzodiazepine derivative, were evaluated in a series of 29 healthy volunteers aged 18 to 72 years, who ingested single 20 mg oral doses. CBZ kinetics were determined from multiple plasma concentrations measured during 7 days after the dose. 2 CB...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1981.tb01281.x
更新日期：1981-11-01 00:00:00
abstract：AIM:We compared the pharmacokinetic (PK) profiles of co-crystal of tramadol-celecoxib (CTC) vs. each reference product (alone and in open combination) after single (first dose) and multiple dosing. METHODS:Healthy adults aged 18-50 years received, under fasted conditions, 15 twice-daily doses of the following treatmen...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/bcp.13428
更新日期：2018-01-01 00:00:00
abstract：AIMS:To study the delivery of 15 mg beclomethasone 17,21-dipropionate (BDP) to the distal part of the small bowel for three oral sustained-release formulations (I-III) and a reference capsule in volunteer ileostomists, and to compare these findings with the in vitro dissolution profiles. METHODS:Two groups of nine ile...
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.1365-2125.1998.00782.x
更新日期：1998-09-01 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：:1. The beta-adrenergic blocking potencies of practolol, ICI 66082, tolamolol, acebutolol, H 93/26, H 87/07, pindolol and Ro 3-4787 were compared with that of propranolol, on human and rat adipocytes. 2. A good correlation was found between the potencies on adipocytes of the two species but not between our results and ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1975.tb02776.x
更新日期：1975-08-01 00:00:00
abstract：:1 From an understanding of the biological fate and hypotensive effect of debrisoquine (D) we have assessed the relative importance of true drug resistance, inappropriately low dosage and non-compliance as causes of apparent resistance to treatment with this drug. 2 Among 37 hypertensive patients prescribed D, eleven (...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1980.tb01072.x
更新日期：1980-04-01 00:00:00
abstract：AIMS:BG00010 is a protein in the glial cell line-derived neurotrophic factor (GDNF) family. It is a selective ligand for the GDNF family receptor alpha-3 (GFRα3) co-receptor that normalizes cellular changes resulting from damage or disease, and potentially alleviates neuropathic pain. The main objectives of this study ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/bcp.12941
更新日期：2016-07-01 00:00:00
abstract：AIMS:Reduced nitric oxide (NO) availability may adversely affect renal perfusion and glomerular filtration. The aim of the present study was to characterize in detail the pharmacological effects of VAS203, an inhibitor of NO synthase, on renal haemodynamics in humans. METHODS:This double-blind, randomized, placebo-con...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/bcp.13870
更新日期：2019-05-01 00:00:00
abstract：AIMS:To investigate the spectrum of toxicity of moclobemide overdose, the occurrence of serotonin toxicity, and to estimate toxicokinetic parameters. METHODS:All moclobemide overdoses presenting over a 10-year period to the Hunter Area Toxicology Service were reviewed. Clinical features, complications, length of stay ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2003.01895.x
更新日期：2003-10-01 00:00:00
abstract：:1 Soluble aspirin, 600 mg and 1200 mg, and placebo were compared in a double-blind, cross-over study in 12 patients with post-operative pain following removal of impacted lower third molars. 2 Significant analgesia after 600 mg aspirin occurred only at 45 min after administration, whereas significant analgesia after 1...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1982.tb01870.x
更新日期：1982-06-01 00:00:00
abstract：:1 Daily treatment of two-kidney clipped renal hypertensive rats with hydrallazine, hydrochlorothiazide (HCTZ) and a new orally active inhibitor of the angiotensin-converting enzyme, captopril (SQ14,225), was correlated with survival rates for up to 9 months. 2 The groups of rats given captopril alone or captopril plus...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1979.tb04696.x
更新日期：1979-01-01 00:00:00
abstract：:1. Mono(ADP-ribosyl)transferase activity has been identified on the external surface of human polymorphonuclear neutrophil leucocytes (PMNs). The enzyme is released from the plasma membrane by phosphoinositide-specific phospholipase C, suggesting a glycosylphosphatidylinositol (GPI) linkage of the enzyme to the plasma...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.1996.37014.x
更新日期：1996-07-01 00:00:00
abstract：:1 The effect of an intravenous bolus of labetalol (0.6-1.6 mg/kg body weight) on central and peripheral haemodynamics was studied in nine subjects with essential hypertension and in eleven subjects with chronic renal disease and hypertension. 2 The BP reduction amounting to 20/13 mmHg was entirely due to the lowering ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1979.tb04764.x
更新日期：1979-04-01 00:00:00
abstract：:1 We have performed a double-blind, randomized, 7-d cross-over study of the thromboxane synthetase inhibitor dazoxiben (UK 37248) in 20 patients with stable coronary heart disease. 2 All patients had a history of exertional angina of greater than two years duration and no patient had suffered a myocardial infarction i...
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.1365-2125.1983.tb02114.x
更新日期：1983-01-01 00:00:00
abstract：AIM:To describe the time to clinical events (death, disability, cognitive impairment and depression) in Parkinson's disease using the time course of disease status and treatment as explanatory variables. METHODS:Disease status based on the Unified Parkinson's Disease Rating Scale (UPDRS) and the time to clinical outco...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2012.04208.x
更新日期：2012-08-01 00:00:00
abstract：:Vertigo is associated with a wide range of vestibular pathologies. It increasingly affects the elderly, with a high cost to society. Solutions include vestibular suppressants and vestibular rehabilitation, which form the mainstay of therapy. Antihistamines represent the largest class of agents used to combat vestibula...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.14046
更新日期：2019-10-01 00:00:00
abstract：AIMS:Paracetamol is frequently involved in intended self-poisoning, and concomitant overdosing of other drugs is commonly reported. The purpose of the study was to investigate further concomitant drug overdose in patients with paracetamol poisoning and to evaluate its effects on the outcome of the paracetamol intoxicat...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2002.01564.x
更新日期：2002-05-01 00:00:00
abstract：AIMS:Ward physicians hold key positions in the course of efforts to reduce drug expenditures in hospitals. This study evaluated the knowledge of German hospital physicians with respect to the daily therapeutic costs of 21 frequently used drugs. METHODS:A questionnaire survey was carried out among 168 ward physicians f...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2001.01336.x
更新日期：2001-04-01 00:00:00
abstract：:Aims We investigated whether venoconstriction by α-adrenoceptor stimulation, and venodilation by β-adrenoceptor stimulation and nitroglycerin are altered in patients with diabetes mellitus (DM). Methods Eight male patients with non insulin-dependent DM and eight age-matched control subjects were included. The patients...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.1999.00915.x
更新日期：1999-04-01 00:00:00
