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 Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Bach B,Hansen JM,Kampmann JP,Rasmussen SN,Skovsted Ldoi
10.2165/00003088-198106050-00005subject
Has Abstractpub_date
1981-09-01 00:00:00pages
389-96issue
5eissn
0312-5963issn
1179-1926journal_volume
6pub_type
杂志文章abstract:: ...
journal_title:Clinical pharmacokinetics
pub_type: 评论,信件
doi:10.1007/s40262-018-0665-2
更新日期:2018-07-01 00:00:00
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
更新日期:2015-10-01 00:00:00
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
更新日期:2018-07-01 00:00:00
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
更新日期:1999-05-01 00:00:00
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
更新日期:2017-04-01 00:00:00
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
更新日期:1984-07-01 00:00:00
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
更新日期:2016-09-01 00:00:00
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
更新日期:1991-03-01 00:00:00
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
更新日期:1990-09-01 00:00:00
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
更新日期:2013-12-01 00:00:00
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
更新日期:2013-04-01 00:00:00
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
更新日期:1991-04-01 00:00:00
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
更新日期:1988-06-01 00:00:00
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
更新日期:1988-12-01 00:00:00
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
更新日期:2005-01-01 00:00:00
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
更新日期:1999-04-01 00:00:00
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
更新日期:2008-01-01 00:00:00
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
更新日期:1999-01-01 00:00:00
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
更新日期:2005-01-01 00:00:00
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
更新日期:2017-08-01 00:00:00
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
更新日期:1994-08-01 00:00:00
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
更新日期:1985-03-01 00:00:00
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
更新日期:1988-06-01 00:00:00
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
更新日期:2009-01-01 00:00:00
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
更新日期:2009-01-01 00:00:00
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
更新日期:2020-11-01 00:00:00
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
更新日期:1997-05-01 00:00:00
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
更新日期:1986-05-01 00:00:00
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
更新日期:2016-06-01 00:00:00
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
更新日期:2020-09-17 00:00:00