Abstract：
AIM:To characterize the romiplostim dose-response in subjects with low or intermediate-1 risk myelodysplastic syndromes (MDS) receiving subcutaneous romiplostim. METHODS:Data from 44 MDS subjects receiving subcutaneous romiplostim (dose range 300-1500 μg week(-1) ) were used to develop a pharmacodynamic model consisting of a romiplostim-sensitive progenitor cell compartment linked to the peripheral blood compartment through four transit compartments representing the maturation in the bone marrow from megakaryocytes to platelets. A kinetics of drug effect model was used to quantify the stimulatory effect of romiplostim on the proliferation of sensitive progenitor cells and pharmacodynamics-mediated disposition was modelled by assuming the kinetics of drug effect constant (kDE ) to be proportional to the change in platelet count relative to baseline. RESULTS:The estimated values (between subject variability) for baseline platelet count, mean transit time, and kDE were 24 × 10(9) l(-1) (47%), 9.6 days (44%) and 0.28 days(-1) , respectively. MDS subjects had a shorter platelet lifespan (42 h) than healthy subjects (257 h). Romiplostim effect was described for responders (78%) and non-responders (22%). The average weekly stimulatory effect of romiplostim on the production rate of sensitive progenitor cells at baseline was 269% per 100 μg week(-1) for responders. Body weight, age, gender and race were not statistically related to romiplostim pharmacodynamic parameters. Visual predictive checks confirmed the model adequacy. CONCLUSION:The time course of platelet counts in MDS subjects receiving subcutaneous administration of escalating doses of romiplostim was characterized and showed a linear dose-response for romiplostim responders to increase the platelet counts.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Perez Ruixo JJ,Doshi S,Wang YM,Mould DRdoi
10.1111/bcp.12041subject
Has Abstractpub_date
2013-06-01 00:00:00pages
1445-54issue
6eissn
0306-5251issn
1365-2125journal_volume
75pub_type
杂志文章abstract：:1. We compare the sensitivity and specificity of chosen outcome criteria in a placebo-controlled, randomised cross-over study of the efficacy of maintenance therapy with the levodopa/carbidopa combination (Sinemet Plus) alone. Patients were characterised by having idiopathic Parkinsonism with no overt fluctuations in ...
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
abstract：:1 The heart rate responses to increasing doses of isoprenaline (n = 6) (during infusion with atropine 0.5 mg/min i.v.) and noradrenaline (n = 5), (during infusion with phentolamine 160 mg/h i.v.) were recorded before and after the intravenous administration of propranolol (15 mg) or metoprolol (15 mg). 2 In the doses ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1982.tb01911.x
更新日期：1982-01-01 00:00:00
abstract：:1 The bronchodilating efficacy and the degree of beta2-adrenoceptor selectivity of rimiterol, salbutamol and isoprenaline were determined in seven subjects who exhibited histamine-induced bronchoconstriction. 2 Rimiterol, 0.5 (high dose) and 0.05 (low dose) mug kg-1 min-1, salbutamol, 0.3 and 0.03 mug kg-1 min-1, isop...
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.1365-2125.1975.tb00470.x
更新日期：1975-02-01 00:00:00
abstract：:1 Cardiovascular responses to intravenous prizidilol hydrochloride (SK&F 92657) 0.86 mg/kg were studied in eight supine resting healthy volunteers. Five subjects were slow and the remaining three were fast acetylators of sulphamethazine. Compared with pre-infusion values, mean resting systolic and diastolic blood pres...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1981.tb01266.x
更新日期：1981-10-01 00:00:00
abstract：:1 Comparison of phenytoin clearance showed a marked increase in people over 65 years of age compared with people under 45 years of age. 2 This difference was apparent if phenytoin was given orally or intravenously. 3 Phenytoin clearance correlated inversely with phenytoin binding and plasma albumin, both of which were...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1975.tb00475.x
更新日期：1975-02-01 00:00:00
abstract：:Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions as a key regulator of cell growth, division and survival. Many haematologic malignancies exhibit elevated or aberrant mTOR activation, supporting the launch of numerous clinical trials aimed at evaluating the potential of single agent m...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.12888
更新日期：2016-11-01 00:00:00
abstract：:1 Human common palmar digital arteries and dorsal metacarpal veins have been studied in vitro to investigate the responses of arterial and venous muscle to hydrallazine, diazoxide, nitroprusside and sodium nitrite. 2 Tissues were removed at autopsy, cut into helical strips and suspended in organ baths under identical ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1981.tb01102.x
更新日期：1981-01-01 00:00:00
abstract：:1. We studied the effects of pre-treatment with oral indomethacin (25 mg four times daily for 3 days) on the pharmacokinetics, haemodynamics and diuretic properties of oral felodipine (10 mg single dose) in 12 healthy male volunteers using a placebo controlled double-blind four-way crossover protocol. 2. Felodipine wi...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1988.tb05295.x
更新日期：1988-11-01 00:00:00
abstract：:Since many factors may alter lung epithelial permeability (LEP) to water soluble molecules, the effect of histamine on the absorption and clearance of inhaled sodium cromoglycate was examined in seven mildly asthmatic patients with hyperresponsive airways and eight normal subjects. The subjects underwent histamine cha...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1992.tb04048.x
更新日期：1992-03-01 00:00:00
abstract：:The kinetics of flecainide after single intravenous (2 mg kg-1) and oral (200 mg) dosing, absolute bioavailability, effects of food and aluminium hydroxide on flecainide absorption and steady-state kinetics following twice daily oral dosing (200 mg) have been evaluated in ten healthy subjects. Absolute bioavailability...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1986.tb02892.x
更新日期：1986-09-01 00:00:00
abstract：:1. Quinidine is a potent inhibitor of the genetically-determined debrisoquine 4-hydroxylation. Oxidation reactions of several other drugs, including the 5-hydroxylation of the new antiarrhythmic drug propafenone, depend on the isozyme responsible for debrisoquine 4-hydroxylation. 2. The effect of quinidine on the debr...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1989.tb05391.x
更新日期：1989-04-01 00:00:00
abstract：AIMS:The aim of this study was to investigate the effect of policosanol on the susceptibility of LDL-C to in vitro lipid peroxidation in human healthy volunteers. METHODS:The effect of policosanol (5 and 10 mg day(-1) on LDL-C oxidation was studied in a double-blind, randomized, placebo-controlled trial conducted in 6...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1046/j.1365-2125.2000.00250.x
更新日期：2000-09-01 00:00:00
abstract：:1 Six healthy male volunteers received a total of 2500 mg of a new cephalosporin antibiotic Ro13-9904 by intramuscular injection in five divided doses at intervals of 12 h. 2 No significant systemic side-effects were observed and this was confirmed haematologically and biochemically. 3 The drug was distributed followi...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1981.tb01188.x
更新日期：1981-08-01 00:00:00
abstract：AIMS:AT9283 is used to treat patients with solid tumours and patients with leukaemia. However, the maximum tolerated dose (MTD) for children with leukaemia remains unknown due to early termination of the Phase I trial. The aim of this study was to develop a population model of AT9283 to describe the pharmacokinetics in...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.13260
更新日期：2017-08-01 00:00:00
abstract：:Cyclophosphamide is an alkylating agent used in the treatment of solid and haematological malignancies and as an immunosuppressive agent. As a prodrug, it is dependent on bioactivation to the active phosphoramide mustard metabolite to elicit its therapeutic effect. This focused review will highlight the evidence for t...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.14031
更新日期：2019-09-01 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：AIMS:Spirometry, plethysmography and impulse oscillometry (IOS) measure different aspects of lung function. These methods have not been compared for their ability to assess long- and short-acting anticholinergic agents. We therefore performed a double-blind, placebo-controlled, four-way cross-over study in 30 healthy s...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1365-2125.2006.02594.x
更新日期：2006-04-01 00:00:00
abstract：AIMS:Homeopathic medicines are frequently purchased over the counter (OTC). Respiratory complaints are the most frequent reason for such purchases. Children with upper respiratory tract infection (URTI) are frequent users of homeopathy. This study investigates the effect of self treatment with one of three self selecte...
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.1365-2125.2005.02336.x
更新日期：2005-04-01 00:00:00
abstract：:A double-blind, placebo-controlled, cross-over trial of quinine in leg cramps occurring at rest was conducted in 22 elderly cramp sufferers. Despite demonstration of impaired quinine elimination in the elderly, prescription of the traditional dose of 300 mg quinine bisulphate at night failed to produce a significant (...
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.1365-2125.1987.tb03076.x
更新日期：1987-04-01 00:00:00
abstract：:Exposure-response (ER) analysis has emerged as an important tool to interpret QT data from thorough QT (TQT) studies and allows the prediction of effects in the targeted patient population. Recently, ER analysis has also been applied to data from early clinical pharmacology studies, such as single and multiple ascendi...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.12068
更新日期：2013-11-01 00:00:00
abstract：:1. Endogenous dopamine, acting through specific receptors on blood vessels, renal tubules and adrenal cortical cells, may play a role in the development and maintenance of the hypertensive state. 2. In hypertensive patients, activation of the DA1-receptor with intravenous fenoldopam produces a rapid and sustained redu...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2125.1990.tb05470.x
更新日期：1990-01-01 00:00:00
abstract：:1 Six previously untreated emergency admissions to hospital with severe hypertension were given oral treatment with labetalol. 2 Pre-treatment diastolic BP exceeded 130 mmHg, and clinical evidence of either accelerated hypertension or encephalopathy was present. 3 Hypotensive response after treatment followed two patt...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1979-01-01 00:00:00
abstract：AIMS:To investigate presence or absence of clinically relevant drug interactions (pharmacokinetic and safety/tolerability) of OBE022 with standard-of-care medicines for preterm labour, enabling coadministration and further clinical development. METHODS:Part A: open-label, randomized, 3-period crossover assessing coadm...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/bcp.13925
更新日期：2019-07-01 00:00:00
abstract：:Ten volunteers carried a 10 mg 24 h -1 transdermal glyceryl trinitrate (GTN) patch for 24 h before moderate exercise. Plasma GTN-concentration increased significantly (P less than 0.05) by 19% to peak value at 15 min. Two hours after patch renewal repeat exercise increased GTN concentration by 56% (P less than 0.001)....
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1991.tb05582.x
更新日期：1991-05-01 00:00:00
abstract：AIMS:To summarize and extend the main conclusions and recommendations relevant to drug management during acute kidney disease (AKD) as agreed at the 16th Acute Disease Quality Initiative (ADQI) consensus conference. METHODS:Using a modified Delphi method to achieve consensus, experts attending the 16th ADQI consensus ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.13449
更新日期：2018-02-01 00:00:00
abstract：:1. The pharmacokinetics of methylprednisolone (MP) were studied in five normal subjects following intravenous doses of 20, 40 and 80 mg methylprednisolone sodium succinate (MPSS) and an oral dose of 20 mg methylprednisolone as 4 x 5 mg tablets. Plasma concentrations of MP and MPSS were measured by both high performanc...
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.1365-2125.1989.tb05366.x
更新日期：1989-03-01 00:00:00
abstract：:The effects of intravenous nicardipine (2.5 mg) on the left ventricular (LV) inotropic state, LV metabolism, and coronary haemodynamics were analysed in 22 patients with angina pectoris. Measurements were made at fixed heart rate (atrial pacing), under basal state, and during a cold pressor test. After nicardipine, co...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1985.tb05158.x
更新日期：1985-01-01 00:00:00
abstract：:1. The efficacy of felodipine a new calcium channel blocker with selective vasodilator activity in the management of severe low output cardiac failure, secondary to coronary heart disease, was determined in 10 patients. 2. Haemodynamic measurements were made at rest and during dynamic exercise and left ventricular fun...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1988.tb05254.x
更新日期：1988-06-01 00:00:00
abstract：:1. The kinetics and effects of ebastine 10 and 50 mg were studied after oral dosing in healthy subjects. 2. The parent drug was extensively metabolised during the first pass to its carboxylic acid derivative, carebastine. 3. The pharmacokinetics of carebastine were linear over the dose range studied and the terminal e...
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.tb05288.x
更新日期：1988-11-01 00:00:00
abstract：:1 This study was designed to compare in a double-blind randomized crossover trial, atenolol, labetalol, metoprolol and pindolol. Considerable differences in dose (atenolol 138 +/- 13 mg daily; labetalol 308 +/- 34 mg daily; metoprolol 234 +/- 22 mg daily; and pindolol 24 +/-2 mg daily were required to produce similar ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1979.tb04774.x
更新日期：1979-04-01 00:00:00
