Prediction of Individual Serum Infliximab Concentrations in Inflammatory Bowel Disease by a Bayesian Dashboard System.

Abstract:

:Despite a robust exposure-response relationship of infliximab in inflammatory bowel disease (IBD), attempts to adjust dosing to individually predicted serum concentrations of infliximab (SICs) are lacking. Compared with labor-intensive conventional software for pharmacokinetic (PK) modeling (eg, NONMEM) dashboards are easy-to-use programs incorporating complex Bayesian statistics to determine individual pharmacokinetics. We evaluated various infliximab detection assays and the number of samples needed to precisely forecast individual SICs using a Bayesian dashboard. We assessed long-term infliximab retention in patients being dosed concordantly versus discordantly with Bayesian dashboard recommendations. Three hundred eighty-two serum samples from 117 adult IBD patients on infliximab maintenance therapy were analyzed by 3 commercially available assays. Data from each assay was modeled using NONMEM and a Bayesian dashboard. PK parameter precision and residual variability were assessed. Forecast concentrations from both systems were compared with observed concentrations. Infliximab retention was assessed by prediction for dose intensification via Bayesian dashboard versus real-life practice. Forecast precision of SICs varied between detection assays. At least 3 SICs from a reliable assay are needed for an accurate forecast. The Bayesian dashboard performed similarly to NONMEM to predict SICs. Patients dosed concordantly with Bayesian dashboard recommendations had a significantly longer median drug survival than those dosed discordantly (51.5 versus 4.6 months, P < .0001). The Bayesian dashboard helps to assess the diagnostic performance of infliximab detection assays. Three, not single, SICs provide sufficient information for individualized dose adjustment when incorporated into the Bayesian dashboard. Treatment adjusted to forecasted SICs is associated with longer drug retention of infliximab.

journal_name

J Clin Pharmacol

authors

Eser A,Primas C,Reinisch S,Vogelsang H,Novacek G,Mould DR,Reinisch W

doi

10.1002/jcph.1069

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

790-802

issue

6

eissn

0091-2700

issn

1552-4604

journal_volume

58

pub_type

杂志文章
  • Clinical utility of ambulatory blood pressure monitoring in target organ complications and equipment choices.

    abstract::Although population studies have demonstrated a relationship between casual office blood pressures and target organ events, the variability of these blood pressure measurements for individual patients has generated an interest in the role of ambulatory blood pressure monitoring for defining the presence of hypertensio...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/j.1552-4604.1992.tb05771.x

    authors: Prisant LM,Bottini PB,Carr AA

    更新日期:1992-07-01 00:00:00

  • Effect of sodium alginate on acid gastroesophageal reflux disease in preterm infants: a pilot study.

    abstract::The objective of this study was to evaluate the effect of the antireflux barrier formed by Na alginate on pH-metry-defined acid reflux events in preterms. Four times/day, 1 mL/kg of Na alginate was administered as an intervention to the preterm infants whose gastroesophageal reflux disease was confirmed by 24-hour pH ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270009338483

    authors: Atasay B,Erdeve O,Arsan S,Türmen T

    更新日期:2010-11-01 00:00:00

  • The effect of various postphlebotomy storage conditions on drug levels.

    abstract::Monitoring drug levels in patients is standard practice in presentday critical care medicine. Clinical laboratories, however, are often unable to assay drug levels immediately following phlebotomy. This may result in blood samples being kept under a variety of storage conditions for nonuniform periods of time. The cur...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1988.tb03212.x

    authors: Colucci RD,Halpern NA,Levy E,McElhinney AJ,Greenstein RJ

    更新日期:1988-08-01 00:00:00

  • Enalapril in the management of hypertension associated with renal artery stenosis.

    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

    pub_type: 杂志文章

    doi:10.1177/009127008702700105

    authors: Canzanello VJ,Madaio MP,Madias NE

    更新日期:1987-01-01 00:00:00

  • Oral antidiabetic drugs: bioavailability assessment of fixed-dose combination tablets of pioglitazone and metformin. Effect of body weight, gender, and race on systemic exposures of each drug.

    abstract::Bioavailability of pioglitazone and metformin, in 2 dose strengths, given either as a fixed-dose combination tablet or as coadministration of commercial tablets (coad), was studied in young healthy subjects in 2 separate studies. In study I (n = 63), single oral doses of 15-mg pioglitazone/500-mg metformin fixed-dose ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,meta分析,随机对照试验

    doi:10.1177/0091270006293755

    authors: Karim A,Slater M,Bradford D,Schwartz L,Zhao Z,Cao C,Laurent A

    更新日期:2007-01-01 00:00:00

  • Contrasting effects of pyrazinoylguanidine and hydrochlorothiazide in patients with renal insufficiency.

    abstract::A single blind crossover study with washout phases showed that pyrazinoylguanidine (PZG) reduced elevated serum concentrations of urea, triglycerides, and cholesterol in patients with renal insufficiency. Pyrazinoylguanidine was saluretic, without affecting serum potassium or glucose concentrations. The onset of PZG's...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1993.tb04703.x

    authors: Beyer KH Jr,Ward TD,Vary JE,Gelarden RT,Knutson DW,Vesell ES

    更新日期:1993-06-01 00:00:00

  • Pharmacokinetic Properties of Nintedanib in Healthy Volunteers and Patients With Advanced Cancer.

    abstract::Nintedanib, a triple angiokinase inhibitor, has undergone clinical investigation for the treatment of solid tumors and idiopathic pulmonary fibrosis. Nintedanib (Vargatef® ) plus docetaxel is approved in the EU for the treatment of patients with adenocarcinoma non-small cell lung cancer (NSCLC) after first-line chemot...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/jcph.752

    authors: Dallinger C,Trommeshauser D,Marzin K,Liesener A,Kaiser R,Stopfer P

    更新日期:2016-11-01 00:00:00

  • The relevance of T-type calcium antagonists: a profile of mibefradil.

    abstract::L- and T-type voltage-dependent transmembrane calcium channels are important for normal functioning of the cardiovascular system. T-type channels are a heterogeneous group, and have physiologic and pathophysiologic relevance in a number of organ systems, including the heart and central nervous system. They appear to b...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/j.1552-4604.1998.tb04804.x

    authors: Glasser SP

    更新日期:1998-08-01 00:00:00

  • Risk-benefit value of inhaled glucocorticoids: a pharmacokinetic/pharmacodynamic perspective.

    abstract::Inhaled glucocorticoids induce therapeutic and adverse systemic effects via the same types of receptors. Analysis of the pharmacokinetic/pharmacodynamic parameters of inhaled glucocorticoids generates a risk-benefit value (RBV). Targeted efficacy with minimal adverse effects helps to quantify an appropriate RBV. High ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1177/0091270003260334

    authors: Rohatagi S,Appajosyula S,Derendorf H,Szefler S,Nave R,Zech K,Banerji D

    更新日期:2004-01-01 00:00:00

  • Pharmacokinetics and safety of solifenacin succinate in healthy young men.

    abstract::The pharmacokinetic profile of solifenacin succinate (YM905; Vesicare), a new once-daily bladder-selective muscarinic receptor antagonist, was examined in 2 controlled trials of healthy young men. A single-dose study evaluated 5-, 10-, 20-, 40-, 60-, 80-, and 100-mg doses. A multidose study evaluated 5-, 10-, 20-, and...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/0091270004267592

    authors: Smulders RA,Krauwinkel WJ,Swart PJ,Huang M

    更新日期:2004-09-01 00:00:00

  • Pharmacokinetic and pharmacodynamic evaluation of triamcinolone acetonide after intravenous, oral, and inhaled administration.

    abstract::Triamcinolone acetonide (TCA) is a corticosteroid that is frequently used in the treatment of asthma. After inhalation, TCA can become systemically available when the inhaled formulation is swallowed, causing undesirable systemic effects. A clinical study was conducted to determine the systemic side effects of TCA aft...

    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.tb04045.x

    authors: Rohatagi S,Hochhaus G,Mollmann H,Barth J,Galia E,Erdmann M,Sourgens H,Derendorf H

    更新日期:1995-12-01 00:00:00

  • The Effect of Age on the Pharmacokinetics of Udenafil in Healthy Subjects.

    abstract::Udenafil, a cyclic guanosine monophosphate-specific phosphodiesterase type 5 inhibitor, has been developed to treat erectile dysfunction. We evaluated the effect of age on the pharmacokinetics and tolerability of udenafil. A single-center, open-label, parallel-group phase 1 study was conducted in healthy adult subject...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.739

    authors: Choi HK,Jung JA,Shon J,Bahng MY,Cho DY,Yeo CW,Kim EY,Shin JG

    更新日期:2016-11-01 00:00:00

  • Pharmacokinetics of esmolol in hepatic disease.

    abstract::Esmolol is an intravenous beta blocker with a short duration of action. The pharmacokinetics of esmolol and its acid metabolite, ASL-8123, were studied in nine patients who had stable, biopsy-proved Laennec's cirrhosis and in three normal volunteer controls. Kinetics were determined after a four-hour continuous infusi...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1987.tb05583.x

    authors: Buchi KN,Rollins DE,Tolman KG,Achari R,Drissel D,Hulse JD

    更新日期:1987-11-01 00:00:00

  • No effect of rosuvastatin on the pharmacokinetics of digoxin in healthy volunteers.

    abstract::The effect of rosuvastatin on the pharmacokinetics of digoxin was assessed in 18 healthy male volunteers in this double-blind, randomized, two-way crossover trial. Volunteers were dosed with rosuvastatin (40 mg once daily) or placebo to steady state before being given a single dose of digoxin 0.5 mg. Blood and urine s...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/0091270002042012008

    authors: Martin PD,Kemp J,Dane AL,Warwick MJ,Schneck DW

    更新日期:2002-12-01 00:00:00

  • Effects of extensive and poor gastrointestinal metabolism on the pharmacodynamics of pravastatin.

    abstract::The enhanced nonenzymatic isomerization of pravastatin to SQ 31,906, a relatively inactive metabolite, has been demonstrated to occur on exposure to gastric acidity in humans. However, the effect of gastric metabolism on the pharmacodynamics of pravastatin has not been studied. In addition, it was hypothesized that so...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1998.tb04432.x

    authors: Ito MK

    更新日期:1998-04-01 00:00:00

  • The influence of intravenous cimetidine dosage regimens on the disposition of theophylline.

    abstract::The influence of the method of cimetidine administration on theophylline disposition was studied in nine healthy, cigarette smoking male volunteers. The treatment phases consisted of: A) theophylline alone, B) theophylline plus intermittent cimetidine therapy (300 mg IV every 6 hr), and C) theophylline in combination ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1989.tb03398.x

    authors: Gutfeld MB,Welage LS,Walawander CA,Wilton JH,Harrison NJ

    更新日期:1989-07-01 00:00:00

  • Efficacy and safety of ketoprofen patch in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled study.

    abstract::This study assessed the efficacy and safety of ketoprofen patch compared with placebo in patients who had rheumatoid arthritis and persistent wrist pain. Patients (N = 676)who had achieved systemic disease control with a disease-modifying antirheumatic drug and/or systemic corticosteroid, but still had persistent wris...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270009355813

    authors: Kawai S,Uchida E,Kondo M,Ohno S,Obata J,Nawata Y,Sugimoto K,Oribe M,Nagaya I

    更新日期:2010-10-01 00:00:00

  • Pharmacology of acetylcholinesterase inhibitors and N-methyl-D-aspartate receptors for combination therapy in the treatment of Alzheimer's disease.

    abstract::The search for effective treatments of Alzheimer's disease (AD) is one of the major challenges facing modern medicine. Acetylcholinesterase (AChE) inhibitors (AChEIs) are effective for the treatment of mild to moderate AD, and memantine, an N-methyl-D-aspartate (NMDA) inhibitor, has been approved for moderate to sever...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1177/0091270006288734

    authors: Geerts H,Grossberg GT

    更新日期:2006-07-01 00:00:00

  • Pharmacokinetic and pharmacodynamic profiles of CS-518, a selective, long-lasting thromboxane synthase inhibitor, after single and multiple oral administration to healthy volunteers.

    abstract::A selective thromboxane (TX) synthase inhibitor, CS-518, was orally administered to healthy male Japanese volunteers and the pharmacokinetic and pharmacodynamic properties were investigated. The time profile of drug concentrations in plasma was determined, and the effects of the drug on platelet aggregation in plasma ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1994.tb03964.x

    authors: Uematsu T,Nagashima S,Inaba H,Mizuno A,Kosuge K,Nakashima M

    更新日期:1994-01-01 00:00:00

  • Clinical microdialysis in skin and soft tissues: an update.

    abstract::Traditionally, plasma or serum drug concentrations have been used for the assessment of bioavailability and bioequivalence. Since in the majority of cases the site of drug action is in the tissue rather than the blood, the use of corresponding free, unbound concentrations in the tissue is a much more meaningful approa...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1177/0091270007312152

    authors: Schmidt S,Banks R,Kumar V,Rand KH,Derendorf H

    更新日期:2008-03-01 00:00:00

  • Clinical pharmacology of bispecific antibody constructs.

    abstract::The confluence of rapid scientific advancements especially in protein engineering and recombinant technology, unmet medical needs, and commercial incentives have led to the development of the next generation of therapeutic proteins. Bispecific antibody constructs are one of the novel strategies that is being pursued, ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/jcph.445

    authors: Rathi C,Meibohm B

    更新日期:2015-03-01 00:00:00

  • Gastrointestinal Tolerability and Absorption of R- Versus R,S-Lipoic Acid in Progressive Multiple Sclerosis: A Randomized Crossover Trial.

    abstract::We compared the gastrointestinal (GI) tolerability and assessed for bioequivalent absorption of R-lipoic acid (LA) in people with progressive multiple sclerosis (MS) in a single-center, double-blind, randomized crossover trial. Participants randomly assigned to formulation sequence took 600 mg of R-LA or 1200 mg of a ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1605

    authors: Cameron M,Taylor C,Lapidus J,Ramsey K,Koop D,Spain R

    更新日期:2020-08-01 00:00:00

  • Relationships of Changes in Pharmacokinetic Parameters of Substrate Drugs in Drug-Drug Interactions on Metabolizing Enzymes and Transporters.

    abstract::A general objective of drug-drug interaction (DDI) studies is to determine whether potential interactions of new molecular entities with concomitantly administered other drugs exist and, if DDIs occur, whether dosage adjustments are required. A typical end point for DDI evaluations is the ratio of area under the plasm...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1104

    authors: Yamazaki S

    更新日期:2018-08-01 00:00:00

  • Effect of CYP2C19 genetic polymorphism on pharmacokinetics and pharmacodynamics of a new proton pump inhibitor, ilaprazole.

    abstract::It is well known that the CYP2C19 genetic polymorphism influences the pharmacokinetics and pharmacodynamics of proton pump inhibitors (PPIs), but no report has addressed the effects on ilaprazole, a newly developed PPI. To investigate the effects of the CYP2C19 genetic polymorphism on the disposition and pharmacodynam...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270011408611

    authors: Cho H,Choi MK,Cho DY,Yeo CW,Jeong HE,Shon JH,Lee JY,Shin JS,Cho M,Kim DY,Shin JG

    更新日期:2012-07-01 00:00:00

  • The role of TNFalpha in ulcerative colitis.

    abstract::Standard of care for ulcerative colitis involves long-term pharmacotherapy or colectomy. Approximately 20% to 30% of patients eventually require a colectomy because patients either do not respond or cannot tolerate the currently available pharmacotherapies. Advances in our knowledge of the pathophysiology of ulcerativ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1177/0091270007301623

    authors: Sands BE,Kaplan GG

    更新日期:2007-08-01 00:00:00

  • Pharmacological modulation of peripheral T and B lymphocytes by a selective sphingosine 1-phosphate receptor-1 modulator.

    abstract::CS-0777 is a selective sphingosine 1-phosphate receptor-1 (S1P(1)) modulator under development for treatment of autoimmune conditions. A randomized, double-blind, placebo-controlled study was conducted to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of CS-0777 in escalat...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270011408728

    authors: Moberly JB,Rohatagi S,Zahir H,Hsu C,Noveck RJ,Truitt KE

    更新日期:2012-07-01 00:00:00

  • Intense management of diabetes mellitus: role of glucose control and antiplatelet agents.

    abstract::Type 2 diabetes has now reached epidemic proportions across the world and is the cause of substantial morbidity and mortality. Patients with diabetes suffer from their mircovascular complications of retinopathy (blindness), nephropathy (renal failure, dialysis), and neuropathy (neropathic pain, trophic ulcers). Howeve...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1177/0091270004263045

    authors: Mudaliar S

    更新日期:2004-04-01 00:00:00

  • Nonsteroidal antiinflammatory drug modulation of behavioral responses to intrathecal N-methyl-D-aspartate, but not to substance P and amino-methyl-isoxazole-propionic acid in the rat.

    abstract::Antinociception by nonsteroidal antiinflammatory drugs, notably diclofenac and S(+)-ibuprofen, has traditionally been attributed to peripheral tissue cyclooxygenase inhibition. This study investigates the potential role of the nitric oxide system for the central antinociceptive effects of diclofenac, S(+)-, and R(-)-i...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:

    authors: Björkman R,Hallman KM,Hedner J,Hedner T,Henning M

    更新日期:1996-12-01 00:00:00

  • The monoamine oxidase type B inhibitor rasagiline in the treatment of Parkinson disease: is tyramine a challenge?

    abstract::Rasagiline is an irreversible monoamine oxidase type B (MAO-B) inhibitor indicated for the treatment of the signs and symptoms of idiopathic Parkinson disease as initial monotherapy and as adjunct therapy to levodopa. Pharmacologic inhibition of monoamine oxidase type A (MAO-A), but not MAO-B, poses a risk of the "che...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1177/0091270011406279

    authors: Chen JJ,Wilkinson JR

    更新日期:2012-05-01 00:00:00

  • Dosing regimen of gentamicin during intermittent peritoneal dialysis.

    abstract::The peritoneal clearance of gentamicin was studied in 11 chronic uremic patients who undergoing intermittent peritoneal dialysis. Gentamicin was significantly removed by peritoneal dialysis with a clearance value of 9.75 +/- 3.78 ml/min. The serum half life was 14.08 +/- 3.57 hr, a value significantly less than that o...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1989.tb03302.x

    authors: Kaojarern S,Arkaravichien W,Indraprasit S,Pummangura C

    更新日期:1989-02-01 00:00:00