A mechanistic approach for the scaling of clearance in children.

Abstract:

BACKGROUND AND OBJECTIVE:Clearance is an important pharmacokinetic concept for scaling dosage, understanding the risks of drug-drug interactions and environmental risk assessment in children. Accurate clearance scaling to children requires prior knowledge of adult clearance mechanisms and the age-dependence of physiological and enzymatic development. The objective of this research was to develop and evaluate ontogeny models that would provide an assessment of the age-dependence of clearance. METHODS:Using in vitro data and/or in vivo clearance values for children for eight compounds that are eliminated primarily by one process, models for the ontogeny of renal clearance, cytochrome P450 (CYP) 3A4, CYP2E1, CYP1A2, uridine diphosphate glucuronosyltransferase (UGT) 2B7, UGT1A6, sulfonation and biliary clearance were developed. Resulting ontogeny models were evaluated using six compounds that demonstrated elimination via multiple pathways. The proportion of total clearance attributed to each clearance pathway in adults was delineated. Each pathway was individually scaled to the desired age, inclusive of protein-binding prediction, and summed to generate a total plasma clearance for the child under investigation. The paediatric age range included in the study was premature neonates to sub-adults. RESULTS:There was excellent correlation between observed and predicted clearances for the model development (R2 = 0.979) and test sets (Q2 = 0.927). Clearance in premature neonates could also be well predicted (development R2 = 0.951; test Q2 = 0.899). CONCLUSION:Paediatric clinical trial development could greatly benefit from clearance scaling, particularly in guiding dosing regimens. Furthermore, since the proportion of clearance via different elimination pathways is age-dependent, information could be gained on the developmental extent of drug-drug interactions.

journal_name

Clin Pharmacokinet

authors

Edginton AN,Schmitt W,Voith B,Willmann S

doi

10.2165/00003088-200645070-00004

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

683-704

issue

7

eissn

0312-5963

issn

1179-1926

pii

4574

journal_volume

45

pub_type

杂志文章
  • Geographical/interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19.

    abstract::The isoenzymes which catalyse the polymorphic hydroxylations of debrisoquine/sparteine and S-mephenytoin are cytochromes P450 2D6 and P450 2C19 (CYP2D6 and CYP2C19), respectively. CYP2D6 is involved in the stereospecific metabolism of several important groups of drugs, for example antiarrhythmics, antidepressants and ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199529030-00005

    authors: Bertilsson L

    更新日期:1995-09-01 00:00:00

  • Pharmacokinetics and clinical efficacy of phenobarbital in asphyxiated newborns treated with hypothermia: a thermopharmacological approach.

    abstract:BACKGROUND AND OBJECTIVES:Therapeutic hypothermia can influence the pharmacokinetics and pharmacodynamics of drugs, the discipline which is called thermopharmacology. We studied the effect of therapeutic hypothermia on the pharmacokinetics of phenobarbital in asphyxiated neonates, and the clinical efficacy and the effe...

    journal_title:Clinical pharmacokinetics

    pub_type: 临床试验,杂志文章

    doi:10.1007/s40262-012-0004-y

    authors: van den Broek MP,Groenendaal F,Toet MC,van Straaten HL,van Hasselt JG,Huitema AD,de Vries LS,Egberts AC,Rademaker CM

    更新日期:2012-10-01 00:00:00

  • Developmental pharmacokinetics of gentamicin in preterm and term neonates: population modelling of a prospective study.

    abstract:BACKGROUND AND OBJECTIVE:Preterm and term newborn infants show wide interindividual variability (IIV) in pharmacokinetic parameters of gentamicin. More extensive knowledge and use of predictive covariates could lead to faster attainment of therapeutic concentrations and a reduced need for concentration monitoring. This...

    journal_title:Clinical pharmacokinetics

    pub_type: 临床试验,杂志文章

    doi:10.2165/00003088-200948040-00003

    authors: Nielsen EI,Sandström M,Honoré PH,Ewald U,Friberg LE

    更新日期:2009-01-01 00:00:00

  • Pharmacokinetics of haloperidol.

    abstract::Haloperidol has been used extensively for the treatment of psychotic disorders, and it has been suggested that the monitoring of plasma haloperidol concentration is clinically useful. Different assay methodologies have been used in research and clinical practice to examine the relationship between response and plasma ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-198917060-00004

    authors: Froemming JS,Lam YW,Jann MW,Davis CM

    更新日期:1989-12-01 00:00:00

  • An updated comparison of drug dosing methods. Part IV: Vancomycin.

    abstract::The resurgence of the use of and interest in vancomycin, in conjunction with the high degree of interpatient variability in its pharmacokinetic profile, has prompted the development of many and varied dosing methods. Several dosing nomograms have been proposed and evaluated, methods which are useful for initial dosing...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199120060-00003

    authors: Pryka RD,Rodvold KA,Erdman SM

    更新日期:1991-06-01 00:00:00

  • The aging liver. Drug clearance and an oxygen diffusion barrier hypothesis.

    abstract::A change in drug clearance with age is considered an important factor in determining the high prevalence of adverse drug reactions associated with prescribing medications for the elderly. Despite this, no general principles have been available to guide drug administration in the elderly, although a substantial body of...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.2165/00003088-199834050-00003

    authors: Le Couteur DG,McLean AJ

    更新日期:1998-05-01 00:00:00

  • Famotidine and theophylline pharmacokinetics. An unexpected cimetidine-like interaction in patients with chronic obstructive pulmonary disease.

    abstract::The results of research studies conducted to date in vitro and in healthy volunteers are practically all concordant in demonstrating the lack of any kind of interference between famotidine and microsomal oxidative metabolism. The pharmacokinetics (elimination half-life, area under the plasma concentration-time curve, ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.2165/00003088-199324030-00006

    authors: Dal Negro R,Pomari C,Turco P

    更新日期:1993-03-01 00:00:00

  • Crushed Versus Integral Tablets of Ticagrelor in ST-Segment Elevation Myocardial Infarction Patients: A Randomized Pharmacokinetic/Pharmacodynamic Study.

    abstract:OBJECTIVE:The objective of this study was to assess the pharmacokinetic and pharmacodynamic behavior of ticagrelor administered either as crushed (in the semi-upright sitting position) or as integral (in the supine position) tablets in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percu...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s40262-015-0320-0

    authors: Alexopoulos D,Barampoutis N,Gkizas V,Vogiatzi C,Tsigkas G,Koutsogiannis N,Davlouros P,Hahalis G,Nylander S,Parodi G,Xanthopoulou I

    更新日期:2016-03-01 00:00:00

  • Multiple-dose non-linear regression analysis program. Aminoglycoside dose prediction.

    abstract::The ability of a new multiple-dose non-linear regression analysis program to predict steady-state aminoglycoside peak and trough serum concentrations was evaluated. 30 patients receiving either amikacin (7), gentamicin (10) or tobramycin (13) were studied. A standard method of prediction which requires the collection ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.2165/00003088-198308050-00006

    authors: Koup JR,Killen T,Bauer LA

    更新日期:1983-09-01 00:00:00

  • Clinical pharmacokinetics and pharmacodynamics and pharmacodynamics of artemether-lumefantrine.

    abstract::The combination of artemether and lumefantrine (benflumetol) is a new and very well tolerated oral antimalarial drug effective even against multidrug-resistant falciparum malaria. The artemether component is absorbed rapidly and biotransformed to dihydroartemisinin, and both are eliminated with terminal half-lives of ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199937020-00002

    authors: White NJ,van Vugt M,Ezzet F

    更新日期:1999-08-01 00:00:00

  • Pharmacokinetic Studies in Neonates: The Utility of an Opportunistic Sampling Design.

    abstract:BACKGROUND AND OBJECTIVE:The use of an opportunistic (also called scavenged) sampling strategy in a prospective pharmacokinetic study combined with population pharmacokinetic modelling has been proposed as an alternative strategy to conventional methods for accomplishing pharmacokinetic studies in neonates. However, th...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.1007/s40262-015-0291-1

    authors: Leroux S,Turner MA,Guellec CB,Hill H,van den Anker JN,Kearns GL,Jacqz-Aigrain E,Zhao W,TINN (Treat Infections in NeoNates) and GRiP (Global Research in Paediatrics) Consortiums.

    更新日期:2015-12-01 00:00:00

  • Renal elimination of amikacin and the aging process.

    abstract:OBJECTIVE:Although amikacin is primarily eliminated via glomerular filtration, drug concentrations are not consistently predicted in all patients. To better describe the relationship between amikacin clearance and both age and renal function, we used a new heuristic approach involving statistical analysis of dependence...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.2165/00003088-200140120-00004

    authors: Ducher M,Maire P,Cerutti C,Bourhis Y,Foltz F,Sorensen P,Jelliffe R,Fauvel JP

    更新日期:2001-01-01 00:00:00

  • Multiple dose pharmacokinetics of a new once daily extended release tolterodine formulation versus immediate release tolterodine.

    abstract:OBJECTIVE:To determine the multiple dose pharmacokinetics of a new extended release (ER) capsule formulation of tolterodine, compared with the existing immediate release (IR) tablet, in healthy volunteers. DESIGN:Nonblind, randomised, 2-way crossover trial. PARTICIPANTS:19 healthy volunteers (7 females, 12 males), me...

    journal_title:Clinical pharmacokinetics

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.2165/00003088-200140030-00006

    authors: Olsson B,Szamosi J

    更新日期:2001-01-01 00:00:00

  • Models for placental transfer studies of drugs.

    abstract::Pregnancy is a specific dynamic state, and the potential usefulness of caring for a disorder in the fetus or the mother is now well established. Previously, pregnant women have been excluded from clinical trials, therefore only a few studies concerning evaluation of the pregestational metabolism or transplacental tran...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199528020-00006

    authors: Bourget P,Roulot C,Fernandez H

    更新日期:1995-02-01 00:00:00

  • Pharmacokinetic drug interactions with anti-ulcer drugs.

    abstract::The safety profile of any pharmacological agent is defined on the basis of its toxicity, tolerability and potential for pharmacokinetic and/or pharmacodynamic interactions with other compounds, which may belong to the same or to a different pharmacological class. Drug-drug interactions are important in clinical practi...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199835020-00003

    authors: Negro RD

    更新日期:1998-08-01 00:00:00

  • Clinical pharmacokinetics of sevoflurane.

    abstract::Sevoflurane is a comparatively recent addition to the range of inhalational anaesthetics which has been recently released for clinical use. In comparison to older inhalational agents such as isoflurane or halothane, the most important property of sevoflurane is its low solubility in the blood. This results in a more r...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199936010-00002

    authors: Behne M,Wilke HJ,Harder S

    更新日期:1999-01-01 00:00:00

  • Population Pharmacokinetics of the BTK Inhibitor Acalabrutinib and its Active Metabolite in Healthy Volunteers and Patients with B-Cell Malignancies.

    abstract:INTRODUCTION:Bruton tyrosine kinase (BTK) is a key component of B-cell receptor signalling, critical for cell proliferation. Acalabrutinib, a selective, covalent BTK inhibitor, recently received an accelerated approval in relapsed/refractory mantle cell lymphoma. This analysis characterized the population pharmacokinet...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1007/s40262-018-0725-7

    authors: Edlund H,Lee SK,Andrew MA,Slatter JG,Aksenov S,Al-Huniti N

    更新日期:2019-05-01 00:00:00

  • Pharmacodynamic, pharmacokinetic and pharmacogenetic aspects of drugs used in the treatment of Alzheimer's disease.

    abstract::With the aging population and its rapidly increasing prevalence, dementia has become an important public health concern in developed and developing countries. To date, the pharmacological treatment is symptomatic and based on the observed neurotransmitter disturbances. The four most commonly used drugs are donepezil, ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.1007/s40262-013-0038-9

    authors: Noetzli M,Eap CB

    更新日期:2013-04-01 00:00:00

  • Pharmacokinetics of antibiotics in pregnancy and labour.

    abstract::Few of the articles published on antibiotics and pregnancy are concerned with pharmacokinetics. It is particularly difficult to evaluate possible alterations in pharmacokinetic parameters that may be due to pregnancy. Most data available have been obtained in connection with abortion or delivery. Such data may not be ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-197904040-00003

    authors: Philipson A

    更新日期:1979-07-01 00:00:00

  • Pharmacokinetics of metformin in girls aged 9 years.

    abstract:BACKGROUND AND OBJECTIVE:Metformin is a biguanide used in the treatment of type 2 diabetes mellitus. In girls with a low birth weight, and early-normal and rapidly progressive puberty, metformin therapy is capable of modifying this outcome, prolonging pubertal growth, increasing height gain, delaying the age at menarch...

    journal_title:Clinical pharmacokinetics

    pub_type: 临床试验,杂志文章

    doi:10.2165/11593970-000000000-00000

    authors: Sánchez-Infantes D,Díaz M,López-Bermejo A,Marcos MV,de Zegher F,Ibáñez L

    更新日期:2011-11-01 00:00:00

  • Population-Pharmacokinetic Modeling of Tildrakizumab (MK-3222), an Anti-Interleukin-23-p19 Monoclonal Antibody, in Healthy Volunteers and Subjects with Psoriasis.

    abstract:BACKGROUND:Tildrakizumab is an anti-interleukin-23p19 monoclonal antibody recently approved for the treatment of chronic plaque psoriasis. METHODS:This analysis characterizes the population pharmacokinetics of subcutaneous tildrakizumab and identifies covariates influencing exposure in 2098 healthy volunteers and subj...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s40262-019-00743-7

    authors: Jauslin P,Kulkarni P,Li H,Vatakuti S,Hussain A,Wenning L,Kerbusch T

    更新日期:2019-08-01 00:00:00

  • Target-Mediated Drug Disposition Population Pharmacokinetics Model of Alirocumab in Healthy Volunteers and Patients: Pooled Analysis of Randomized Phase I/II/III Studies.

    abstract:BACKGROUND AND OBJECTIVE:Proprotein convertase subtilisin/kexin type 9 inhibition with monoclonal antibodies such as alirocumab significantly reduces low-density lipoprotein-cholesterol levels ± other lipid-lowering therapies. We aimed to develop and qualify a population pharmacokinetics (PopPK) model for alirocumab in...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,meta分析

    doi:10.1007/s40262-016-0505-1

    authors: Djebli N,Martinez JM,Lohan L,Khier S,Brunet A,Hurbin F,Fabre D

    更新日期:2017-10-01 00:00:00

  • Clinical pharmacology of 5-fluorouracil.

    abstract::5-Fluorouracil, first introduced as a rationally synthesized anticancer agent 30 years ago, continues to be widely used in the management of several common malignancies including cancer of the colon, breast and skin. This drug, an analogue of the naturally occurring pyrimidine uracil, is metabolised via the same metab...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-198916040-00002

    authors: Diasio RB,Harris BE

    更新日期:1989-04-01 00:00:00

  • Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs.

    abstract::Consistent with its highest abundance in humans, cytochrome P450 (CYP) 3A is responsible for the metabolism of about 60% of currently known drugs. However, this unusual low substrate specificity also makes CYP3A4 susceptible to reversible or irreversible inhibition by a variety of drugs. Mechanism-based inhibition of ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-200544030-00005

    authors: Zhou S,Yung Chan S,Cher Goh B,Chan E,Duan W,Huang M,McLeod HL

    更新日期:2005-01-01 00:00:00

  • An Extension of Janmahasatian's Fat-Free Mass Model for Universal Application Across Populations of Different Ethnicities.

    abstract:BACKGROUND:Fat-free mass (FFM)-based dose scaling is increasingly being adopted in clinical pharmacology. Given the complexities with the measurement of FFM in clinical practice, choosing an appropriate equation for FFM is critical for accurate dose scaling. Janmahasatian's FFM model (FFMJan) has largely remained the p...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.1007/s40262-020-00883-1

    authors: Sinha J,Al-Sallami HS,Duffull SB

    更新日期:2020-09-01 00:00:00

  • Drug interactions with cisapride: clinical implications.

    abstract::Cisapride, a prokinetic agent, has been used for the treatment of a number of gastrointestinal disorders, particularly gastro-oesophageal reflux disease in adults and children. Since 1993, 341 cases of ventricular arrhythmias, including 80 deaths, have been reported to the US Food and Drug Administration. Marketing of...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-200039010-00004

    authors: Michalets EL,Williams CR

    更新日期:2000-07-01 00:00:00

  • A Mechanism-Based Population Pharmacokinetic Analysis Assessing the Feasibility of Efavirenz Dose Reduction to 400 mg in Pregnant Women.

    abstract:BACKGROUND:Reducing the dose of efavirenz can improve safety, reduce costs, and increase access for patients with HIV infection. According to the World Health Organization, a similar dosing strategy for all patient populations is desirable for universal roll-out; however, it remains unknown whether the 400 mg daily dos...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.1007/s40262-018-0642-9

    authors: Schalkwijk S,Ter Heine R,Colbers AC,Huitema ADR,Denti P,Dooley KE,Capparelli E,Best BM,Cressey TR,Greupink R,Russel FGM,Mirochnick M,Burger DM

    更新日期:2018-11-01 00:00:00

  • The use of other drugs to allow a lower dosage of cyclosporin to be used. Therapeutic and pharmacoeconomic considerations.

    abstract::Since its discovery in 1970, and introduction into clinical practice in 1978, cyclosporin has become the most important immunosuppressive drug used to prevent organ transplant rejection. This has been achieved by virtue of the improved graft survival rates and adverse effect profiles in patients when compared with tha...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199732050-00002

    authors: Jones TE

    更新日期:1997-05-01 00:00:00

  • Pharmacokinetics of long acting propranolol. Implications for therapeutic use.

    abstract::Beta-adrenoceptor antagonists are among the most commonly prescribed classes of drugs. They are indicated for the treatment of diseases such as hypertension and angina pectoris, in which long term therapy is often required. Since many beta-adrenoceptor antagonists have short plasma elimination half-lives, divided dail...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-198713010-00003

    authors: Nace GS,Wood AJ

    更新日期:1987-07-01 00:00:00

  • Population pharmacokinetic modelling and estimation of dosing strategy for NXY-059, a nitrone being developed for stroke.

    abstract:BACKGROUND AND OBJECTIVES:NXY-059 (disufenton sodium, Cerovive, a nitrone with neuroprotective and free radical trapping properties (in experimental stroke) is under development for the treatment of acute stroke. The objectives of this study were to develop a population pharmacokinetic model for NXY-059 in acute stroke...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.2165/00003088-200544080-00007

    authors: Jönsson S,Cheng YF,Edenius C,Lees KR,Odergren T,Karlsson MO

    更新日期:2005-01-01 00:00:00