Disposition of antipyrine and phenytoin correlated with age and liver volume in man.

Abstract:

:The half-life and metabolic clearance rate (MCR) of antipyrine and phenytoin were determined in 14 young (mean age: 28.8 +/- 8.3 (SD) years] and in 14 elderly [mean age: 83.5 +/- 7.1 (SD) years] subjects and correlated with liver volume, which was determined by ultrasonic scanning, to see if an age-dependent difference in drug metabolism could be explained by a reduced liver weight with age. The size of the liver was smaller in the elderly subjects even when related to decreased body surface. A significant decrease in serum albumin in the elderly compared with the younger group was also noted. The half-life of antipyrine was significantly longer in the elderly than in the younger group, 756 +/- 318 and 465 +/- 110 minutes, respectively, and the MCR was correspondingly lower in the elderly even when calculated per litre of live volume, 22.8 +/- 7.8 and 36.3 +/- 8.9ml/minute/L liver volume, respectively. No significant differences in the 2 age groups were found in half-life and total clearance of phenytoin, but a reduced free phenytoin clearance was demonstrated in the elderly (240 +/- 92ml/minute/L liver volume) compared with the younger (325 +/- 81ml/minute/L liver volume) group. No significant correlation was found between liver volume and the half-life of antipyrine and phenytoin. However, a significant correlation was demonstrated between liver volume and MCR of antipyrine as well as between total and free clearance of phenytoin. No correlation was found between the half-lives of the 2 drugs, while a significant correlation existed between the clearance values. It is suggested that the age-dependent reduction in drug clearance is due not only to a smaller liver volume, but it also a result of a reduced capacity of the liver microsomes per unit of liver in the elderly. With regard to age-dependent changes in drug metabolism, the protein binding of the actual drug has to be taken into consideration.

journal_name

Clin Pharmacokinet

authors

Bach B,Hansen JM,Kampmann JP,Rasmussen SN,Skovsted L

doi

10.2165/00003088-198106050-00005

subject

Has Abstract

pub_date

1981-09-01 00:00:00

pages

389-96

issue

5

eissn

0312-5963

issn

1179-1926

journal_volume

6

pub_type

杂志文章
  • Author's Reply to Reith: "Morbidly Obese Patients Exhibit Increased CYP2E1-Mediated Oxidation of Acetaminophen".

    abstract:: ...

    journal_title:Clinical pharmacokinetics

    pub_type: 评论,信件

    doi:10.1007/s40262-018-0665-2

    authors: van Rongen A,Välitalo PAJ,Knibbe CAJ

    更新日期:2018-07-01 00:00:00

  • A Compartmental Analysis for Morphine and Its Metabolites in Young Children After a Single Oral Dose.

    abstract:BACKGROUND AND OBJECTIVES:Currently, the majority of the surgical procedures performed in paediatric hospitals are done on a day care basis, with post-operative pain being managed by caregivers at home. Pain after discharge of these post-operative children has historically been managed with oral codeine in combination ...

    journal_title:Clinical pharmacokinetics

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/s40262-015-0256-4

    authors: Velez de Mendizabal N,Jimenez-Mendez R,Cooke E,Montgomery CJ,Dawes J,Rieder MJ,Aleksa K,Koren G,Jacobo-Cabral CO,Gonzalez-Ramirez R,Castañeda-Hernandez G,Carleton BC

    更新日期:2015-10-01 00:00:00

  • Prediction of Free from Total Mycophenolic Acid Concentrations in Stable Renal Transplant Patients: A Population-Based Approach.

    abstract:BACKGROUND:A population pharmacokinetic (PK) protein-binding model was developed to (1) predict free mycophenolic acid (fMPA) based on total MPA (tMPA) concentrations in renal transplant patients, to establish the therapeutic range of fMPA through pharmacokinetic-pharmacodynamic studies; and (2) provide a guideline for...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.1007/s40262-017-0603-8

    authors: Colom H,Andreu F,van Gelder T,Hesselink DA,de Winter BCM,Bestard O,Torras J,Cruzado JM,Grinyó JM,Lloberas N

    更新日期:2018-07-01 00:00:00

  • The efficiency concept in pharmacodynamics.

    abstract::The classic approach to describe the pharmacological response to a drug is to analyse its concentration-effect relationship, using a variety of possible models such as maximum effect (Emax) models or sigmoid Emax models. The aim of this review is to discuss an alternative way of describing the pharmacological effect i...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199936050-00005

    authors: Alván G,Paintaud G,Wakelkamp M

    更新日期:1999-05-01 00:00:00

  • Regional Differences in Serotonin Transporter Occupancy by Escitalopram: An [11C]DASB PK-PD Study.

    abstract:BACKGROUND AND OBJECTIVE:Escitalopram is one of the most commonly prescribed selective serotonin reuptake inhibitors (SSRIs). It is thought to act by blocking the serotonin transporter (SERT). However, its dose-SERT occupancy relationship is not well known, so it is not clear what level of SERT blockade is achieved by ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.1007/s40262-016-0444-x

    authors: Kim E,Howes OD,Kim BH,Chon MW,Seo S,Turkheimer FE,Lee JS,Lee YS,Kwon JS

    更新日期:2017-04-01 00:00:00

  • Pharmacokinetic drug interactions with theophylline.

    abstract::Since up to 90% of a theophylline dose is biotransformed, drugs influencing microsomal enzyme systems in the liver may affect the elimination of theophylline. Other integrated mechanisms (e.g. hepatic uptake) may also be altered by concurrent administration of other drugs. Whatever the mechanism, the interaction may b...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-198409040-00002

    authors: Jonkman JH,Upton RA

    更新日期:1984-07-01 00:00:00

  • Cellular Uptake of Glucocerebrosidase in Gaucher Patients Receiving Enzyme Replacement Treatment.

    abstract:BACKGROUND:Enzyme replacement therapy (ERT) is currently the standard treatment for patients with Gaucher disease type I (GD1), but the pharmacokinetics have hardly been studied. This study aimed to quantify in vivo enzyme activity in peripheral leukocytes from patients receiving long-term treatment with imiglucerase o...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.1007/s40262-016-0387-2

    authors: Gras-Colomer E,Martínez-Gómez MA,Moya-Gil A,Fernandez-Zarzoso M,Merino-Sanjuan M,Climente-Martí M

    更新日期:2016-09-01 00:00:00

  • Pharmacokinetic and pharmacodynamic properties of histamine H2-receptor antagonists. Relationship between intrinsic potency and effective plasma concentrations.

    abstract::Histamine H2-receptor antagonists are a unique class of compounds. Pharmacologically they are characterised as a family by their ability to inhibit the secretion of gastric acid, and kinetically they are classified as a family by their similarity in absorption, distribution and elimination. All the H2-receptor antagon...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199120030-00004

    authors: Lin JH

    更新日期:1991-03-01 00:00:00

  • Clinical pharmacokinetics of ketoprofen and its enantiomers.

    abstract::Ketoprofen, a potent nonsteroidal anti-inflammatory drug (NSAID) of the 2-arylpropionic acid class, has been used clinically for over 15 years in Europe, and has recently been introduced in the United States. Although it possesses a chiral centre, with only the S-enantiomer possessing beneficial pharmacological activi...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199019030-00004

    authors: Jamali F,Brocks DR

    更新日期:1990-09-01 00:00:00

  • Differences in cytochrome p450-mediated pharmacokinetics between chinese and caucasian populations predicted by mechanistic physiologically based pharmacokinetic modelling.

    abstract:BACKGROUND:International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines emphasize the need for better understanding of the influence of ethnicity on drug response to minimize duplication of clinical studies, thereby expediting drug approval. OBJ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.1007/s40262-013-0089-y

    authors: Barter ZE,Tucker GT,Rowland-Yeo K

    更新日期:2013-12-01 00:00:00

  • Effect of hepatic and renal impairment on the pharmacokinetics of dalcetrapib: altered distribution of the active thiol?

    abstract:BACKGROUND AND OBJECTIVE:Dalcetrapib, a cholesteryl ester transfer protein (CETP) modulator, is a thioester pro-drug that is rapidly hydrolysed to generate a pharmacologically active thiol. The thiol covalently binds to plasma proteins as mixed disulfides, extensively distributes into plasma lipoprotein fractions, and ...

    journal_title:Clinical pharmacokinetics

    pub_type: 临床试验,杂志文章

    doi:10.1007/s40262-013-0035-z

    authors: Phelan M,Anzures-Cabrera J,Carlile DJ,Rowell L,Kuhlmann O,Arold G,Robson R,Bentley D

    更新日期:2013-04-01 00:00:00

  • Covariance analysis of laboratory variance in steady-state serum phenytoin concentrations.

    abstract::Inpatients (n = 57) on long term prophylaxis with 2 oral phenytoin preparations were followed up via monthly checks of serum drug concentrations. Duplicate serum aliquots were submitted to 2 laboratories, and covariance analysis was used to estimate laboratory error. The laboratory-associated variance of examinations ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.2165/00003088-199120040-00007

    authors: Costeff H,Groswasser Z,Soroker N,van Belle G

    更新日期:1991-04-01 00:00:00

  • The altered pharmacokinetics and pharmacodynamics of drugs commonly used in critically ill patients.

    abstract::The critically ill patient occupies an increasing amount of time and bed space in modern hospital practice, and also commands increasing expenditure. Drug therapy in these patients has, in the past, been based on data derived from healthy volunteers, fit anaesthetised patients undergoing minor operative procedures, or...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-198814060-00003

    authors: Bodenham A,Shelly MP,Park GR

    更新日期:1988-06-01 00:00:00

  • Clinical pharmacokinetics of doxycycline and minocycline.

    abstract::Doxycycline and minocycline are second-generation tetracyclines. They are readily absorbed, distributed throughout the organism as a function of their lipophilicity and eliminated in both the urine and the faeces. The influence of age, renal disease, malnutrition and hyperlipidaemia is reviewed, together with the main...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-198815060-00001

    authors: Saivin S,Houin G

    更新日期:1988-12-01 00:00:00

  • The fentanyl HCl patient-controlled transdermal system (PCTS): an alternative to intravenous patient-controlled analgesia in the postoperative setting.

    abstract::Inadequate pain control in the postoperative period not only contributes to patient discomfort, but also causes physiological changes that may result in increased risk of myocardial ischaemia, deep vein thrombosis and pulmonary embolism. These events complicate postoperative recovery and may lead to longer hospital st...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-200544001-00002

    authors: Sinatra R

    更新日期:2005-01-01 00:00:00

  • Clinical pharmacokinetics and pharmacodynamics of buspirone, an anxiolytic drug.

    abstract::Buspirone is an anxiolytic drug given at a dosage of 15 mg/day. The mechanism of action of the drug is not well characterised, but it may exert its effect by acting on the dopaminergic system in the central nervous system or by binding to serotonin (5-hydroxytryptamine) receptors. Following a oral dose of buspirone 20...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199936040-00003

    authors: Mahmood I,Sahajwalla C

    更新日期:1999-04-01 00:00:00

  • New insulin analogues and routes of delivery: pharmacodynamic and clinical considerations.

    abstract::Analogues of human insulin have been developed to more closely replicate the physiology of meal-related and basal insulin secretion. Three rapid-acting analogues and two basal analogues are available for clinical use. Insulin aspart and insulin lispro have nearly identical pharmacokinetic and pharmacodynamic profiles ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-200847090-00003

    authors: Roach P

    更新日期:2008-01-01 00:00:00

  • Clinical implications of indapamide sustained release 1.5 mg in hypertension.

    abstract::Recent international guidelines on the detection, clinical assessment and management of patients with hypertension have highlighted a number of themes that should be incorporated into routine clinical practice. First, although antihypertensive therapy is having a major impact on reducing the incidence of coronary hear...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199937001-00004

    authors: Donnelly R

    更新日期:1999-01-01 00:00:00

  • Role of cytochrome P450 activity in the fate of anticancer agents and in drug resistance: focus on tamoxifen, paclitaxel and imatinib metabolism.

    abstract::Although activity of cytochrome P450 isoenzymes (CYPs) plays a major role in the fate of anticancer agents in patients, there are relatively few clinical studies that evaluate drug metabolism with therapeutic outcome. Nevertheless, many clinical reports in various non-oncology fields have shown the dramatic importance...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-200544040-00002

    authors: Rochat B

    更新日期:2005-01-01 00:00:00

  • Population Pharmacokinetics and Exploratory Pharmacodynamics of Lorazepam in Pediatric Status Epilepticus.

    abstract:BACKGROUND:Lorazepam is one of the preferred agents used for intravenous treatment of status epilepticus (SE). We combined data from two pediatric clinical trials to characterize the population pharmacokinetics of intravenous lorazepam in infants and children aged 3 months to 17 years with active SE or a history of SE....

    journal_title:Clinical pharmacokinetics

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1007/s40262-016-0486-0

    authors: Gonzalez D,Chamberlain JM,Guptill JT,Cohen-Wolkowiez M,Harper B,Zhao J,Capparelli EV,Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee.

    更新日期:2017-08-01 00:00:00

  • Clinical pharmacokinetics of pravastatin.

    abstract::The hypolipidaemic agent pravastatin differs from other US Food and Drug Administration (FDA)-approved HMG-CoA reductase inhibitors (e.g. lovastatin and simvastatin) because it has greater hydrophilicity, as a result of the hydroxyl group attached to its decalin ring. The hydrophilic nature of pravastatin accounts for...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199427020-00002

    authors: Quion JA,Jones PH

    更新日期:1994-08-01 00:00:00

  • Clinical pharmacokinetics of the salicylates.

    abstract::The use of salicylates in rheumatic diseases has been established for over 100 years. The more recent recognition of their modification of platelet and endothelial cell function has lead to their use in other areas of medicine. Aspirin (acetylsalicylic acid) is still the most commonly used salicylate. After oral admin...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-198510020-00004

    authors: Needs CJ,Brooks PM

    更新日期:1985-03-01 00:00:00

  • Pharmacokinetics and blood pressure effects of felodipine in elderly hypertensive patients. A comparison with young healthy subjects.

    abstract::The pharmacokinetics and antihypertensive effects of felodipine, a new dihydropyridine calcium channel blocker, were studied in elderly hypertensive patients, 67 to 79 years of age and in young healthy subjects, 20 to 34 years of age following oral administration of 5 mg twice daily to steady-state. A single intraveno...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.2165/00003088-198814060-00004

    authors: Landahl S,Edgar B,Gabrielsson M,Larsson M,Lernfelt B,Lundborg P,Regårdh CG

    更新日期:1988-06-01 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

  • Population pharmacokinetics and dosing recommendations for cisplatin during intraperitoneal peroperative administration: development of a limited sampling strategy for toxicity risk assessment.

    abstract:BACKGROUND:Ovarian cancer is the leading cause of gynaecological cancer-related death in Western countries. Intraperitoneal (IP) peroperative chemotherapy is an interesting therapeutic option. However, very few data are available regarding pharmacokinetics and especially population pharmacokinetics. PATIENTS AND METHO...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.2165/00003088-200948030-00003

    authors: Royer B,Jullien V,Guardiola E,Heyd B,Chauffert B,Kantelip JP,Pivot X

    更新日期:2009-01-01 00:00:00

  • Maintenance Immunosuppression in Solid Organ Transplantation: Integrating Novel Pharmacodynamic Biomarkers to Inform Calcineurin Inhibitor Dose Selection.

    abstract::Calcineurin inhibitors, the primary immunosuppressive therapy used to prevent alloreactivity of transplanted organs, have a narrow therapeutic index. Currently, treatment is individualized based on clinical assessment of the risk of rejection or toxicity guided by trough concentration monitoring. Advances in immune mo...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.1007/s40262-020-00923-w

    authors: Leino AD,Pai MP

    更新日期:2020-11-01 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

  • Pharmacokinetic drug interactions of commonly used anticancer drugs.

    abstract::With the use of combination chemotherapy as well as a wide range of symptomatic therapies (e.g. analgesics and antiemetics) for the treatment of patients with cancer, the field of oncology practises polypharmacy to an extreme degree. The risk for a drug interaction under these conditions is high, and the pharmacologic...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-198611030-00004

    authors: Balis FM

    更新日期:1986-05-01 00:00:00

  • Predicting Drug Extraction in the Human Gut Wall: Assessing Contributions from Drug Metabolizing Enzymes and Transporter Proteins using Preclinical Models.

    abstract::Intestinal metabolism can limit oral bioavailability of drugs and increase the risk of drug interactions. It is therefore important to be able to predict and quantify it in drug discovery and early development. In recent years, a plethora of models-in vivo, in situ and in vitro-have been discussed in the literature. T...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.1007/s40262-015-0351-6

    authors: Peters SA,Jones CR,Ungell AL,Hatley OJ

    更新日期:2016-06-01 00:00:00

  • Physiologic Indirect Response Modeling to Describe Buprenorphine Pharmacodynamics in Newborns Treated for Neonatal Opioid Withdrawal Syndrome.

    abstract:BACKGROUND AND OBJECTIVE:Buprenorphine has been shown to be effective in treating infants with neonatal opioid withdrawal syndrome. However, an evidence-based buprenorphine dosing strategy has not been established in the treatment of neonatal opioid withdrawal syndrome because of a lack of exposure-response data. The a...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.1007/s40262-020-00939-2

    authors: Mizuno T,McPhail BT,Kamatkar S,Wexelblatt S,Ward L,Christians U,Akinbi HT,Vinks AA

    更新日期:2020-09-17 00:00:00