Abstract：
:Relationships between tocilizumab exposure and response were evaluated using data from 4 phase III studies. Increased tocilizumab exposure was associated with improvements in Disease Activity Score using 28 joints (DAS28) and American College of Rheumatology (ACR) criteria and with a decrease in inflammation markers. A population pharmacokinetic/pharmacodynamic (PKPD) model was developed to describe data from 2 studies. An indirect-response model with a sigmoid E(max) (maximal drug effect) inhibitory drug effect on DAS28 "production" rate adequately described the relationship between tocilizumab concentration and DAS28. Mean minimum serum tocilizumab concentration at steady state was greater than the EC(50) (concentration at which 50% of E(max) on DAS28 is reached) with the 8-mg/kg dose but not with the 4-mg/kgdose. Simulations within a large rheumatoid arthritis (RA) population showed that DAS remission rates were 38% for 8 mg/kg and 24% for 4 mg/kg. Tocilizumab was more potent in RA patients with higher baseline interleukin-6 levels, but this effect was not clinically significant. Other covariates (eg, presence of neutralizing antitocilizumab antibodies) did not demonstrate a clinically meaningful effect on tocilizumab DAS28 dose-response relationships. These data support clinical observations that tocilizumab 8 mg/kg is more effective than 4 mg/kg in reducing disease activity.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Levi M,Grange S,Frey Ndoi
10.1177/0091270012437585subject
Has Abstractpub_date
2013-02-01 00:00:00pages
151-9issue
2eissn
0091-2700issn
1552-4604journal_volume
53pub_type
杂志文章,随机对照试验abstract：:Experiments were performed on humans to study the blunting on the diuretic action of furosemide by prostaglandin synthetase inhibitors. Maximal water diuresis was instituted. At the peak of urine flow, clearance periods were performed during baseline conditions and repeated after the injection of aspirin and, subseque...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1980.tb01718.x
更新日期：1980-07-01 00:00:00
abstract：:Enalapril maleate (MK-421) is a new non-sulfhydryl-containing converting-enzyme inhibitor that has been shown to be effective and well tolerated in patients with essential hypertension. Data on its effectiveness and safety in patients with renovascular hypertension are limited and have involved predominantly short-ter...
journal_title：Journal of clinical pharmacology
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doi：10.1177/009127008702700105
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abstract：:Chemotherapy-induced nausea and vomiting (CINV) is a common treatment-related adverse event that negatively impacts the quality of life of cancer patients. During pediatric drug development, extrapolation of efficacy from adult to pediatric populations is a pathway that can minimize the exposure of children to unneces...
journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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doi：10.1002/j.1552-4604.1990.tb03590.x
更新日期：1990-11-01 00:00:00
abstract：:Cannabinoids, including smoked marijuana and delta9-tetrahydrocannabinol (THC) (dronabinol, Marinol), have been used to treat human immunodeficiency virus-1 (HIV)-associated anorexia and weight loss. Concerns have been raised, however, that these compounds might have adverse effects on the immune system of subjects wi...
journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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doi：10.1002/j.1552-4604.1983.tb01793.x
更新日期：1983-10-01 00:00:00
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1994.tb04726.x
更新日期：1994-12-01 00:00:00
abstract：:Procainamide administration often results in excessively high serum N-acetylprocainamide (NAPA) concentrations and subtherapeutic serum procainamide concentrations. Inhibition of N-acetylation of procainamide may prevent accumulation of excessive NAPA while maintaining therapeutic serum procainamide concentrations. Th...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/j.1552-4604.1995.tb04135.x
更新日期：1995-09-01 00:00:00
abstract：:A population pharmacokinetic (PPK) model of pomalidomide was developed and the influence of demographic and disease-related covariates on PPK parameters was assessed based on data from 6 clinical trials of pomalidomide (dose range, 0.5-10 mg) in healthy participants (n = 96) and patients with multiple myeloma (MM; n =...
journal_title：Journal of clinical pharmacology
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doi：10.1002/jcph.455
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
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更新日期：2014-01-01 00:00:00
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journal_title：Journal of clinical pharmacology
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doi：10.1177/00912709922008515
更新日期：1999-09-01 00:00:00
abstract：:A new polymeric matrix technology provides a sustained-release formulation of diltiazem hydrochloride (diltiazem SR) suitable for once-daily therapy. The efficacy and safety of diltiazem SR were evaluated in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. After a single-blind, placeb...
journal_title：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：10.1002/j.1552-4604.1992.tb03887.x
更新日期：1992-09-01 00:00:00
abstract：:The primary objective of this study was to identify intravenous regimens of tipifarnib that would mimic the systemic exposure obtained after the current twice-daily oral administration of tipifarnib. After determination of an intravenous dose that 6 subjects with advanced cancer could tolerate, another 26 subjects wer...
journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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doi：10.1002/j.1552-4604.1998.tb04419.x
更新日期：1998-03-01 00:00:00
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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更新日期：1990-12-01 00:00:00
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journal_title：Journal of clinical pharmacology
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abstract：:This study evaluated the pharmacodynamics and pharmacokinetics of once-daily dosing of warfarin at steady state when taken concomitantly with once-daily doses of duloxetine. Healthy subjects with a stable international normalized ratio (INR) of 1.5 to 2.0 on an individualized fixed dose of warfarin (2-9 mg) in period ...
journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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abstract：:Current dosing recommendations for rivaroxaban advocate dosage reduction in patients with moderate to severe renal impairment and avoidance of concomitant strong inhibitors of CYP3A or P-glycoprotein. However, rivaroxaban dosing in patients with mild renal impairment taking concomitant moderate inhibitors of CYP3A and...
journal_title：Journal of clinical pharmacology
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abstract：:Intravenous amiodarone is an effective agent for the treatment of recurrent ventricular fibrillation and hemodynamically unstable ventricular tachycardia. PM101 Premixed Injection is a new formulation of intravenous amiodarone that uses a cyclodextrin to maintain amiodarone in the aqueous phase. Eighty-eight subjects ...
journal_title：Journal of clinical pharmacology
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abstract：:Glomerular filtration rate (GFR) is routinely used as a surrogate endpoint for the development of investigational drugs in clinical trials. GFR and staging of chronic kidney disease are typically assessed by measuring the concentration of endogenous serum biomarkers such as albumin and creatinine. However, creatinine ...
journal_title：Journal of clinical pharmacology
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更新日期：2018-10-01 00:00:00
