Individualized Dosing With High Inter-Occasion Variability Is Correctly Handled With Model-Informed Precision Dosing-Using Rifampicin as an Example.

Abstract:

:Rifampicin exhibits complexities in its pharmacokinetics (PK), including high inter-occasion variability (IOV), which is challenging for dose individualization. Model-informed precision dosing (MIPD) can be used to optimize individual doses. In this simulation-based study we investigated the magnitude of IOV in rifampicin PK on an exposure level, the impact of not acknowledging IOV when performing MIPD, and the number of sampling occasions needed to forecast the dose. Subjects with drug-susceptible tuberculosis (TB) were simulated from a previously developed population PK model. To explore the magnitude of IOV, the area under the plasma concentration-time curve from time zero up to 24 h (AUC0-24h) after 35 mg/kg in the typical individual was simulated for 1,000 sampling occasions at steady-state. The impact of ignoring IOV for dose predictions was investigated by comparing the prediction error of a MIPD approach including IOV to an approach ignoring IOV. Furthermore, the number of sampling occasions needed to predict individual doses using a MIPD approach was assessed. The AUC0-24h in the typical individual varied substantially between simulated sampling occasions [95% prediction interval (PI): 122.2 to 331.2 h mg/L], equivalent to an IOV in AUC0-24h of 25.8%, compared to an inter-individual variability of 25.4%. The median of the individual prediction errors using a MIPD approach incorporating IOV was 0% (75% PI: -14.6% to 0.0%), and the PI for the individual prediction errors was narrower with than without IOV (median: 0%, 75% PI: -14.6% to 20.0%). The most common target dose in this population was forecasted correctly in 95% of the subjects when IOV was included in MIPD. In subjects where doses were not predicted optimally, a lower dose was predicted compared to the target, which is favorable from a safety perspective. Moreover, the imprecision (relative root mean square error) and bias in predicted doses using MIPD with IOV decreased statistically significant when a second sampling occasion was added (difference in imprecision: -9.1%, bias: -7.7%), but only marginally including a third (difference in imprecision: -0.1%, bias: -0.1%). In conclusion, a large variability in exposure of rifampicin between occasions was shown. In order to forecast the individual dose correctly, IOV must be acknowledged which can be achieved using a MIPD approach with PK information from at least two sampling occasions.

journal_name

Front Pharmacol

authors

Keutzer L,Simonsson USH

doi

10.3389/fphar.2020.00794

subject

Has Abstract

pub_date

2020-05-27 00:00:00

pages

794

issn

1663-9812

journal_volume

11

pub_type

杂志文章
  • Mutations Defining Patient Cohorts With Elevated PD-L1 Expression in Gastric Cancer.

    abstract::The immunotherapy agent pembrolizumab has been approved for gastric cancer (GC) patients with recurrent or advanced disease who are PD-L1 positive. Mutations in the primary lesion may drive the expression of immune targets thereby priming the tumor to therapeutic sensitivity. In this study, we aimed to uncover mutatio...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.01522

    authors: Menyhárt O,Pongor LS,Győrffy B

    更新日期:2019-01-08 00:00:00

  • Cysteine Proteases: Modes of Activation and Future Prospects as Pharmacological Targets.

    abstract::Proteolytic enzymes are crucial for a variety of biological processes in organisms ranging from lower (virus, bacteria, and parasite) to the higher organisms (mammals). Proteases cleave proteins into smaller fragments by catalyzing peptide bonds hydrolysis. Proteases are classified according to their catalytic site, a...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2016.00107

    authors: Verma S,Dixit R,Pandey KC

    更新日期:2016-04-25 00:00:00

  • Sensorimotor gating impairments induced by MK-801 treatment may be reduced by tolerance effect and by familiarization in monkeys.

    abstract::Dizocilpine (MK-801) is a non-competitive NMDA antagonist that induces schizophreniclike effects. It is therefore widely used in experimental models of schizophrenia including prepulse inhibition (PPI) impairments in rodents. Nevertheless, MK-801 has never been tested in monkeys on a PPI paradigm. In order to evaluate...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2015.00204

    authors: Saletti PG,Maior RS,Hori E,Nishijo H,Tomaz C

    更新日期:2015-09-22 00:00:00

  • A Significant Association Between Rhein and Diabetic Nephropathy in Animals: A Systematic Review and Meta-Analysis.

    abstract::Background: Rhein is considered to have beneficial influence on diabetic nephropathy. Animal experiments suggested that the mechanisms of rhein against diabetic nephropathy may involve many processes, but the credibility of the evidence is unclear. Therefore, we conducted systematic review and meta-analysis of pre-cli...

    journal_title:Frontiers in pharmacology

    pub_type:

    doi:10.3389/fphar.2019.01473

    authors: Hu HC,Zheng LT,Yin HY,Tao Y,Luo XQ,Wei KS,Yin LP

    更新日期:2019-12-13 00:00:00

  • Increased Levels of miRNA-146a in Serum and Histologic Samples of Patients with Uveal Melanoma.

    abstract::Purpose: To analyze MiRs expression in serum of UM patients, respect to healthy donors, and to compare this data with MiRs expressed in formalin-fixed, paraffin-embedded UM samples. Methods: Expression profile of 754 miRNAs was performed in serum of patients with uveal melanoma who underwent primary enucleation. The l...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2016.00424

    authors: Russo A,Caltabiano R,Longo A,Avitabile T,Franco LM,Bonfiglio V,Puzzo L,Reibaldi M

    更新日期:2016-11-15 00:00:00

  • Periplaneta americana Extracts Accelerate Liver Regeneration via a Complex Network of Pathways.

    abstract::Successful recovery from hepatectomy is partially contingent upon the rate of residual liver regeneration. The traditional Chinese medicines known as Periplaneta americana extracts (PAEs) positively influence wound healing by promoting tissue repair. However, the effect of PAEs on liver regeneration is unknown. We use...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.01174

    authors: Zou Y,Zhang M,Zeng D,Ruan Y,Shen L,Mu Z,Zou J,Xie C,Yang Z,Qian Z,Xu R,Li S,Kang Q,Zou H,Zhao S,Liu L,Wang K,Wang X,Zhang X

    更新日期:2020-07-31 00:00:00

  • Anxiolytic and Antiepileptic Properties of the Aqueous Extract of Cissus quadrangularis (Vitaceae) in Mice Pilocarpine Model of Epilepsy.

    abstract::Cissus quadrangularis (C. quadrangularis) is a plant of the Vitaceae family known for its anticonvulsant effects in traditional medicine. The objective of this study was to elucidate the anxiolytic and antiepileptic effects of aqueous extract of C. quadrangularis. The mice were divided into different groups and treate...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.00751

    authors: Moto FCO,Arsa'a A,Ngoupaye GT,Taiwe GS,Njapdounke JSK,Kandeda AK,Nkantchoua GCN,Omam Omam JP,Pale S,Kouemou NE,Ayissi Mbomo ER,Pahaye DB,Ojong L,Mairara V,Ngo Bum E

    更新日期:2018-07-17 00:00:00

  • Antiamoebic Activity of Adenophyllum aurantium (L.) Strother and Its Effect on the Actin Cytoskeleton of Entamoeba histolytica.

    abstract::In Mexico, the Adenophyllum aurantium (L.) Strother plant is consumed as an infusion to treat intestinal diseases such as amoebiasis, which is an endemic health problem in Mexico and other countries. However, the effect of A. aurantium on Entamoeba histolytica, the causative agent of amoebiasis, is unknown. An aerial ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2016.00169

    authors: Herrera-Martínez M,Hernández-Ramírez VI,Hernández-Carlos B,Chávez-Munguía B,Calderón-Oropeza MA,Talamás-Rohana P

    更新日期:2016-06-27 00:00:00

  • Cyclic nucleotide permeability through unopposed connexin hemichannels.

    abstract::Cyclic adenosine monophosphate (cAMP) is a well-known intracellular and intercellular second messenger. The membrane permeability of such molecules has potential importance for autocrine-like or paracrine-like delivery. Here experiments have been designed to demonstrate whether gap junction hemichannels, composed of c...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2013.00075

    authors: Valiunas V

    更新日期:2013-06-06 00:00:00

  • Drynaria fortunei Promoted Angiogenesis Associated With Modified MMP-2/TIMP-2 Balance and Activation of VEGF Ligand/Receptors Expression.

    abstract::Background and Purpose:Drynaria fortunei J. Sm (D. fortunei), known as Gu-Sui-Bu, is used in traditional Chinese medicine to treat common injuries, including bone fractures and bruising. The specific functional mechanisms of the angiogenic and endothelial cell migration properties of D. fortunei are currently unclear....

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.00979

    authors: Huang ST,Chang CC,Pang JS,Huang HS,Chou SC,Kao MC,You HL

    更新日期:2018-09-21 00:00:00

  • Medicinal Plants and Natural Products Used in Cataract Management.

    abstract::Cataract is the leading reason of blindness worldwide and is defined by the presence of any lens opacities or loss of transparency. The most common symptoms of cataract are impaired vision, decreased contrast sensitivity, color disturbance, and glare. Oxidative stress is among the main mechanisms involved in the devel...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2019.00466

    authors: Tewari D,Samoilă O,Gocan D,Mocan A,Moldovan C,Devkota HP,Atanasov AG,Zengin G,Echeverría J,Vodnar D,Szabo B,Crişan G

    更新日期:2019-06-13 00:00:00

  • Selective Serotonin Reuptake Inhibitor Pharmaco-Omics: Mechanisms and Prediction.

    abstract::Selective serotonin reuptake inhibitors (SSRIs) are a standard of care for the pharmacotherapy of patients suffering from Major Depressive Disorder (MDD). However, only one-half to two-thirds of MDD patients respond to SSRI therapy. Recently, a "multiple omics" research strategy was applied to identify genetic differe...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2020.614048

    authors: Nguyen TTL,Liu D,Ho MF,Athreya AP,Weinshilboum R

    更新日期:2021-01-11 00:00:00

  • A probabilistic model of human variability in physiology for future application to dose reconstruction and QIVIVE.

    abstract::The risk assessment of environmental chemicals and drugs is undergoing a paradigm shift in approach which seeks the full replacement of animal testing with high throughput, mechanistic, in vitro systems. This new approach will be reliant on the measurement in vitro, of concentration-dependent responses where prolonged...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2015.00213

    authors: McNally K,Loizou GD

    更新日期:2015-10-12 00:00:00

  • Long Non-Coding RNA in Drug Resistance of Non-Small Cell Lung Cancer: A Mini Review.

    abstract::Lung cancer is one of main causes of cancer mortality and 83% of lung cancer cases are classified as non-small cell lung cancer (NSCLC). Patients with NSCLC usually have a poor prognosis and one of the leading causes is drug resistance. With the progress of drug therapy, the emergence and development of drug resistanc...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2019.01457

    authors: Sun R,Wang R,Chang S,Li K,Sun R,Wang M,Li Z

    更新日期:2019-12-18 00:00:00

  • Osteoinductivity and Antibacterial Properties of Strontium Ranelate-Loaded Poly(Lactic-co-Glycolic Acid) Microspheres With Assembled Silver and Hydroxyapatite Nanoparticles.

    abstract::Bone-related infection rates are 4-64% in long open bone fractures and nearly 1% in joint-related surgeries. Treating bone infections and infection-related bone loss is very important. The present study prepared strontium ranelate (SR)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (PM) with assembled silver...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.00368

    authors: Mao Z,Li Y,Yang Y,Fang Z,Chen X,Wang Y,Kang J,Qu X,Yuan W,Dai K,Yue B

    更新日期:2018-04-18 00:00:00

  • Composition and Functionality of Lipid Emulsions in Parenteral Nutrition: Examining Evidence in Clinical Applications.

    abstract::Lipid emulsions (LEs), an integral component in parenteral nutrition (PN) feeding, have shifted from the primary aim of delivering non-protein calories and essential fatty acids to defined therapeutic outcomes such as reducing inflammation, and improving metabolic and clinical outcomes. Use of LEs in PN for surgical a...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2020.00506

    authors: Sadu Singh BK,Narayanan SS,Khor BH,Sahathevan S,Abdul Gafor AH,Fiaccadori E,Sundram K,Karupaiah T

    更新日期:2020-04-29 00:00:00

  • A Simple Clinical Pre-procedure Risk Model for Predicting Thrombocytopenia Associated With Periprocedural Use of Tirofiban in Patients Undergoing Percutaneous Coronary Intervention.

    abstract::Background: No risk model for predicting thrombocytopenia associated with periprocedural tirofiban exposure is available. The purpose of this study was to develop a simple clinical pre-procedure risk model based on pre-procedural characteristics for early prediction of thrombocytopenia before patients were exposed to ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.01456

    authors: Yi YH,Yin WJ,Gu ZC,Fang WJ,Li DY,Hu C,Liu K,Ma RR,Zhou LY

    更新日期:2018-12-10 00:00:00

  • Pentameric Ligand-Gated Ion Channels as Pharmacological Targets Against Chronic Pain.

    abstract::Chronic pain is a common detrimental condition that affects around 20% of the world population. The current drugs to treat chronic pain states, especially neuropathic pain, have a limited clinical efficiency and present significant adverse effects that complicates their regular use. Recent studies have proposed new th...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2020.00167

    authors: Lara CO,Burgos CF,Moraga-Cid G,Carrasco MA,Yévenes GE

    更新日期:2020-03-03 00:00:00

  • The High "Cost" of Experimental Drugs Obtained Through Health Litigation in Brazil.

    abstract:Background:Brazilian patients have legal right to access unlicensed medicines undergoing clinical research, if there is evidence of efficacy and safety. This study investigated the occurrence of serious adverse events related to very high-cost medicines from clinical studies, expanded access and compassionate use progr...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.00752

    authors: da Silva RE,Lima EDC,Novaes MRCG,Osorio-de-Castro CGS

    更新日期:2020-05-19 00:00:00

  • New and paradoxical roles of matrix metalloproteinases in the tumor microenvironment.

    abstract::Processes such as cell proliferation, angiogenesis, apoptosis, or invasion are strongly influenced by the surrounding microenvironment of the tumor. Therefore, the ability to change these surroundings represents an important property through which tumor cells are able to acquire specific functions necessary for tumor ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2012.00140

    authors: Noël A,Gutiérrez-Fernández A,Sounni NE,Behrendt N,Maquoi E,Lund IK,Cal S,Hoyer-Hansen G,López-Otín C

    更新日期:2012-07-17 00:00:00

  • Beta2-Adrenergic Receptor Polymorphisms and Haplotypes Associate With Chronic Pain in Sickle Cell Disease.

    abstract::Pain in sickle cell disease (SCD) is severe, variable, and inadequately comprehended. The β2-adrenergic receptor (ADRB2) is critical in mediating neurotransmitter response in the sympathetic nervous system. In this association study, we examined 16 single nucleotide polymorphisms (SNPs) covering 5'-UTR and coding regi...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2019.00084

    authors: Jhun EH,Sadhu N,Hu X,Yao Y,He Y,Wilkie DJ,Molokie RE,Wang ZJ

    更新日期:2019-02-07 00:00:00

  • Antioxidant and Anti-tyrosinase Activities of Phenolic Extracts from Rape Bee Pollen and Inhibitory Melanogenesis by cAMP/MITF/TYR Pathway in B16 Mouse Melanoma Cells.

    abstract::Rape bee pollen possesses many nutritional and therapeutic properties because of its abundant nutrimental and bioactive components. In this study, free (FPE) and bound (BPE) phenolic extracts of rape bee pollen were obtained, phenolic and flavonoid contents were determined, and composition of phenolic acids was analyz...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2017.00104

    authors: Sun L,Guo Y,Zhang Y,Zhuang Y

    更新日期:2017-03-09 00:00:00

  • Nuciferine Ameliorates Inflammatory Responses by Inhibiting the TLR4-Mediated Pathway in Lipopolysaccharide-Induced Acute Lung Injury.

    abstract::Acute lung injury (ALI) is a complex syndrome with sepsis occurring in critical patients, who usually lack effective therapy. Nuciferine is a primary bioactive component extracted from the lotus leaf, and it displays extensive pharmacological functions, including anti-cancer, anti-inflammatory, and antioxidant propert...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2017.00939

    authors: Wu H,Yang Y,Guo S,Yang J,Jiang K,Zhao G,Qiu C,Deng G

    更新日期:2017-12-21 00:00:00

  • A practical approach to communicating benefit-risk decisions of medicines to stakeholders.

    abstract:PURPOSE:The importance of a framework for a systematic structured assessment of the benefits and risks has been established, but in addition, it is necessary that the benefit-risk decisions and the processes to derive those decisions are documented and communicated to various stakeholders for accountability. Hence ther...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2015.00099

    authors: Leong J,Walker S,Salek S

    更新日期:2015-06-11 00:00:00

  • Mitochondria as Potential Targets in Alzheimer Disease Therapy: An Update.

    abstract::Alzheimer disease (AD) is a progressive and deleterious neurodegenerative disorder that affects mostly the elderly population. At the moment, no effective treatments are available in the market, making the whole situation a compelling challenge for societies worldwide. Recently, novel mechanisms have been proposed to ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2019.00902

    authors: Cenini G,Voos W

    更新日期:2019-08-23 00:00:00

  • Screening and Identification of Key Biomarkers in Acquired Lapatinib-Resistant Breast Cancer.

    abstract::Lapatinib, targeting the human epidermal growth factor receptor family members HER1 and HER2, has been approved by the US Food and Drug Administration for use in metastatic HER2-positive breast cancer. However, resistance to lapatinib remains a common challenge to HER2-positive metastatic breast cancer. Until now, the...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.577150

    authors: Bao S,Chen Y,Yang F,Sun C,Yang M,Li W,Huang X,Li J,Wu H,Yin Y

    更新日期:2020-09-04 00:00:00

  • Recombinant Human Endostatin Suppresses Mouse Osteoclast Formation by Inhibiting the NF-κB and MAPKs Signaling Pathways.

    abstract::Rheumatoid arthritis is an autoimmune disease characterized by synovial hyperplasia and progressive joint destruction. As reported previously, recombinant human endostatin (rhEndostatin) is associated with inhibition of joint bone destruction present in rat adjuvant-induced arthritis; however, the effect of rhEndostat...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2016.00145

    authors: Chen N,Gao RF,Yuan FL,Zhao MD

    更新日期:2016-06-01 00:00:00

  • Antioxidant, Anti-Inflammatory and Antiproliferative Effects of the Vitis vinifera L. var. Fetească Neagră and Pinot Noir Pomace Extracts.

    abstract::The pathophysiology of inflammation and oxidative stress generated during different types of cancers and anticancer treatments is well documented. Traditionally, grape pomace is used for animal feed, organic fertilizers, ethanol production or is disposed as waste. Because grape pomace is a rich source of antioxidant c...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.00990

    authors: Balea ŞS,Pârvu AE,Pârvu M,Vlase L,Dehelean CA,Pop TI

    更新日期:2020-07-03 00:00:00

  • Serum Concentrations of Cholinesterase Inhibitors in Patients With Alzheimer's Dementia Are Frequently Below the Recommended Levels.

    abstract:Background:Acetylcholinesterase inhibitors (AChE-I) are recommended for the treatment of cognitive symptoms but also of behavioral and psychological symptoms in dementia. They are widely used not only in Alzheimer's disease, but also in other forms of dementia. Efficacy of treatment might depend on serum concentration ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.00691

    authors: Ortner M,Stange M,Schneider H,Schroeder C,Buerger K,Müller C,Dorn B,Goldhardt O,Diehl-Schmid J,Förstl H,Steimer W,Grimmer T

    更新日期:2020-05-21 00:00:00

  • Acute Digital Ischemia After Arterial Injection of Crushed Zolpidem Tablets: Role of Microcrystalline Cellulose? A Case Report.

    abstract::Literature is scarce on acute ischemia after intra-arterial injection of crushed tablets and no effective medical treatment against the progression of lesions is reported. The only factor able to modify the outcome is the delay between injection and management by a specialized vascular team. Moreover the risk of necro...

    journal_title:Frontiers in pharmacology

    pub_type:

    doi:10.3389/fphar.2020.560382

    authors: Détriché G,Goudot G,Khider L,Galloula A,Guillet M,Lillo-Le Louët A,Messas E,Mirault T

    更新日期:2020-12-03 00:00:00