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 (LOS) and intensive care (ICU) admission rate were extracted from a standardized, prospectively collected database. Comparisons were made between moclobemide alone and moclobemide with a serotonergic coingestant poisoning. Serotonin toxicity was defined by a combination of Sternbach's criteria and a clinical toxicologist's diagnosis. In five patients serial moclobemide concentrations were measured. Time to maximal plasma concentration (Tmax), peak plasma concentration (Cmax) and terminal elimination half-lives were estimated. RESULTS:Of 106 included patients, 33 ingested moclobemide alone, 21 ingested moclobemide with another serotonergic agent (in some cases in therapeutic doses) and 52 ingested moclobemide with a nonserotonergic agent. Eleven (55%) of 21 patients coingesting a serotonergic drug developed serotonin toxicity, which was significantly more than one (3%) of 33 moclobemide-alone overdoses (odds ratio 35, 95% confidence interval 4, 307; P < 0.0001). In six of these 21 cases severe serotonin toxicity developed with temperature >38.5 degrees C and muscle rigidity requiring intubation and paralysis. The 21 patients had a significantly increased LOS (34 h) compared with moclobemide alone overdoses (12 h) (P < 0.0001) and a significantly increased ICU admission rate of 57% vs. 3% (P < 0.0001). Time to peak plasma concentration was delayed in two patients where prepeak samples were obtained. Cmax increased slightly with dose, but all three patients ingesting > or = 6 g vomited or had charcoal. The mean elimination half-life of moclobemide in the five patients in whom serial moclobemide concentrations were measured was 6.3 h and elimination was first order in all cases. There was no evidence of a dose-dependent increase in half-life. CONCLUSIONS:The effects of moclobemide alone in overdose are minor, even with massive ingestions. However, moclobemide overdose in combination with a serotonergic agent (even in normal therapeutic doses) can cause severe serotonin toxicity. The elimination half-life is prolonged by two to four times in overdose, compared with that found in healthy volunteers given therapeutic doses. This may be a result of wide interindividual variation in overall elimination, also seen with therapeutic doses, but appears not to be due to saturation of normal elimination pathways.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Isbister GK,Hackett LP,Dawson AH,Whyte IM,Smith AJdoi
10.1046/j.1365-2125.2003.01895.xkeywords:
subject
Has Abstractpub_date
2003-10-01 00:00:00pages
441-50issue
4eissn
0306-5251issn
1365-2125pii
1895journal_volume
56pub_type
杂志文章abstract::1. Relative rates of absorption of enteric and non-enteric preparations of prednisolone were measured in five renal transplant recipients. 2. The absorption of the enteric coated preparation is delayed and the peak plasma concentration is much lower than that attained using the same dose of the uncoated material. 3. T...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1975.tb02777.x
更新日期:1975-08-01 00:00:00
abstract::1 Measurements have been made of steady state serum phenytoin concentration, serum half-life of (14)C-labelled phenytoin, and the urinary ratio of the major metabolite of phenytoin to the unchanged drug (p-HPPH: DPH ratio) in epileptic patients on and off sulthiame therapy. 2 Starting sulthiame treatment produced an i...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1974.tb00207.x
更新日期:1974-02-01 00:00:00
abstract:AIMS:Dexloxiglumide is a new CCK(1) receptor antagonist under investigation for treatment of functional gastrointestinal disorders and is metabolized by CYP3A4 and CYP2C9. The objectives of these two separate randomized, two-period, two-treatment crossover studies were to investigate the effects of steady-state ketocon...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/j.1365-2125.2005.02465.x
更新日期:2005-11-01 00:00:00
abstract::The binding of disopyramide (DP) and mono-N-dealkyldisopyramide (MND) was measured by equilibrium dialysis in spiked whole blood (10 mumol l-1 DP or MND) from 50 patients having a serum concentration of alpha 1-acid glycoprotein (AAG) ranging from 0.40 to 3.14 g l-1, as well as in whole blood from five healthy subject...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1986.tb02888.x
更新日期:1986-09-01 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. We attempted to collect information on the metabolism and production of angiotensins (ANG) in different vascular beds in humans by constant i.v. infusion of mono-iodinated [125I]-ANG I into subjects with essential hypertension, at the time of renal vein catheterization as part of the diagnostic work-up for renovasc...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1989.tb03586.x
更新日期:1989-01-01 00:00:00
abstract::Cefpiramide is a new parenteral cephalosporin mainly excreted in the bile. Eight patients with cholestasis and 11 healthy subjects received a single 1 g i.v. dose. Cefpiramide concentrations in plasma and urine were measured by h.p.l.c. and plasma binding was determined by ultrafiltration. Total clearance of cefpirami...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1994.tb04278.x
更新日期:1994-03-01 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:AIMS:To develop a population pharmacokinetic model for mycophenolic acid (MPA) in children with idiopathic nephrotic syndrome (INS) treated with mycophenolate mofetil (MMF), identify covariates that explain variability and determine the Bayesian estimator of the area under the concentration-time curve over 12 h (AUC(0-...
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.1365-2125.2010.03615.x
更新日期:2010-04-01 00:00:00
abstract:AIMS:Azathioprine, mercaptopurine and thioguanine are commonly used to treat autoimmune disorders, leukaemia and solid organ transplantation. However, azathiopurine and its metabolites can also cause adverse reactions such as myelosuppression. These manifestations may be attributed to polymorphisms or mutations in the ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2009.03405.x
更新日期:2009-07-01 00:00:00
abstract:AIMS:To determine whether and to what extent bronchoconstriction affects plasma concentrations of fluticasone and budesonide following inhalation. METHODS:Twenty people with mild asthma inhaled 1000 microg fluticasone (Accuhaler) plus 800 microg budesonide (Turbohaler) on two visits. On one occasion, prior to drug inh...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2007.02856.x
更新日期:2007-10-01 00:00:00
abstract:AIMS:Hypertension is a common comorbidity of patients with COVID-19, SARS or HIV infection. Such patients are often concomitantly treated with antiviral and antihypertensive agents, including ritonavir and nifedipine. Since ritonavir is a strong inhibitor of CYP3A and nifedipine is mainly metabolized via CYP3A, the com...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14684
更新日期:2020-12-02 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. Since salt depletion stimulates the renal prostaglandin system to maintain renal function, the effects of indomethacin and ibuprofen upon renal haemodynamics, electrolyte excretion and renin release were examined in eight healthy male volunteers on a salt restricted diet, before and after frusemide administration. ...
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.1365-2125.1990.tb03641.x
更新日期:1990-03-01 00:00:00
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...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb03841.x
更新日期:1990-11-01 00:00:00
abstract::1. The study was performed to determine the sensitivity and short-term and day-to-day variability of a novel technique based on laser interferometry of ocular fundus pulsations and of non-invasive methods for the quantification of haemodynamic drug effects. An additional aim was to assess sex differences in haemodynam...
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.1365-2125.1995.tb04462.x
更新日期:1995-04-01 00:00:00
abstract:AIMS:This study investigates paediatric drug dosage guidelines with the aim of investigating their agreement with body surface area (BSA) scaling principles. METHODS:A total of 454 drug dosage guidelines listed in the AMH-CDC 2015 were examined. Data extracted included the administration, frequency and dose per age br...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13511
更新日期:2018-05-01 00:00:00
abstract:AIMS:Antithrombin is increasingly used in paediatric patients, yet there are few age-specific pharmacokinetic data to guide dosing. We aimed to describe the pharmacokinetic profile of human (plasma-derived) antithrombin concentrate in paediatric patients. METHODS:A 5-year retrospective review was performed of patients...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13359
更新日期:2017-11-01 00:00:00
abstract:AIMS:To describe the pharmacokinetic-pharmacodynamic (PK-PD) characteristics of the direct thrombin inhibitor dabigatran in hip replacement patients by assessing coagulation parameters activated partial thromboplastin time (aPTT) and ecarin clotting time (ECT), interindividual variability and factors affecting PD respo...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2006.02667.x
更新日期:2006-11-01 00:00:00
abstract::1 Improvement in physical performance, based on exercise tolerance, self-assessed work and physician-rated functional capacities, is proposed as a measure of efficacy of anti-anginal therapy in the rehabilitation of the cardiac patient. 2 Improved physical performance parallels changes in frequency of anginal attacks ...
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.1365-2125.1979.tb04686.x
更新日期:1979-01-01 00:00:00
abstract:PURPOSE:Prescribed daily dose (PDD), the number of doses prescribed to be taken per day, is used to calculate medication adherence using pharmacy claims data. PDD can be substituted by (i) one dose per day (1DD), (ii) an estimate based on the 75th percentile of days taken by patients to refill a script (PDD75 ) or (iii...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14468
更新日期:2020-07-08 00:00:00
abstract:AIMS:Generic products can be regarded as therapeutically equivalent and switchable with the reference product. However, switchability between generics is unknown, as direct comparisons between generics are not performed. The aim of this study was to investigate the bioequivalence between generic clopidogrel products by...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13997
更新日期:2019-09-01 00:00:00
abstract::Children are not small adults. However, the main thesis of this review will be that children's responses to drugs have much in common with the responses in adults and indeed in other mammals. Often, it is assumed that drug effects differ in children but in reality this perception often arises because the drugs have no...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2005.02445.x
更新日期:2005-06-01 00:00:00
abstract::Thiol compounds have been reported to abolish hypoxanthine/xanthine oxidase induced luminol chemiluminescence and this effect has been attributed to scavenging of superoxide (O2-)/(H2O2) produced from hypoxanthine/xanthine oxidase. Yet other workers have reported that thiol compounds have shown little, if any, reactiv...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1995.tb05730.x
更新日期:1995-06-01 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:AIMS:Previous pharmacokinetic characterization of a transporter probe cocktail containing digoxin (P-gp), furosemide (OAT1, OAT3), metformin (OCT2, MATE1, MATE2-K) and rosuvastatin (OATP1B1, OATP1B3, BCRP) in healthy subjects showed increases in rosuvastatin systemic exposure compared to rosuvastatin alone. In this tri...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.13609
更新日期:2018-09-01 00:00:00
abstract::Since hepatic clearance of ICG is reduced by H2-receptor antagonists in normal subjects, it has been suggested that they reduce liver blood flow. We have studied the effect of intravenous ranitidine on ICG clearance in twelve patients with chronic liver disease. Wedged and free hepatic venous pressure were measured be...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb04973.x
更新日期:1983-08-01 00:00:00
abstract::We have developed a method of monitoring plasma concentrations of antiepileptic drugs which uses salivary samples, and is suitable for home monitoring in children. To validate the method, paired plasma and saliva samples from 39 children aged between 2 and 15 years were assayed for carbamazepine and its active metabol...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1993.tb05700.x
更新日期:1993-03-01 00:00:00
abstract:AIMS:To establish whether the SCN1A IVS5-91 G > A polymorphism of the SCN1A gene, which encodes the neuronal sodium channel alpha subunit, affects responsiveness to the antiepileptic drugs (AEDS) carbamazepine and/or phenytoin. METHODS:SCN1A IVS5-91 G > A polymorphism was genotyped in 228 Japanese epileptic patients t...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2008.03203.x
更新日期:2008-08-01 00:00:00
abstract::The ability to recall details of current and prior drug therapy was evaluated in two studies employing a total of 94 patients with inflammatory polyarthritis. Ten per cent of patients were unable to completely recall the names of their current anti-inflammatory drugs and eighty-three per cent of patients to completely...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02417.x
更新日期:1984-06-01 00:00:00