Abstract：
:The opioid class of drugs, a large group, is mainly used for the treatment of acute and chronic persistent pain. All are eliminated from the body via metabolism involving principally CYP3A4 and the highly polymorphic CYP2D6, which markedly affects the drug's function, and by conjugation reactions mainly by UGT2B7. In many cases, the resultant metabolites have the same pharmacological activity as the parent opioid; however in many cases, plasma metabolite concentrations are too low to make a meaningful contribution to the overall clinical effects of the parent drug. These metabolites are invariably more water soluble and require renal clearance as an important overall elimination pathway. Such metabolites have the potential to accumulate in the elderly and in those with declining renal function with resultant accumulation to a much greater extent than the parent opioid. The best known example is the accumulation of morphine-6-glucuronide from morphine. Some opioids have active metabolites but at different target sites. These are norpethidine, a neurotoxic agent, and nordextropropoxyphene, a cardiotoxic agent. Clinicians need to be aware that many opioids have active metabolites that will become therapeutically important, for example in cases of altered pathology, drug interactions and genetic polymorphisms of drug-metabolizing enzymes. Thus, dose individualisation and the avoidance of adverse effects of opioids due to the accumulation of active metabolites or lack of formation of active metabolites are important considerations when opioids are used.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Coller JK,Christrup LL,Somogyi AAdoi
10.1007/s00228-008-0570-ysubject
Has Abstractpub_date
2009-02-01 00:00:00pages
121-39issue
2eissn
0031-6970issn
1432-1041journal_volume
65pub_type
杂志文章,评审abstract：BACKGROUND:Zolmitriptan is a 5HT(1B/1D) receptor agonist effective in the acute treatment of migraine. Clinical trials in the USA and Europe have demonstrated the optimal oral therapeutic dose to be 2.5 mg. The 2.5-mg oral tablet has recently been licensed in Japan. OBJECTIVE:To compare the pharmacokinetics of zolmitr...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1007/s00228-002-0461-6
更新日期：2002-07-01 00:00:00
abstract：OBJECTIVE:To evaluate the effect of the CYP2D6 genotype on the pharmacokinetics of tropisetron in healthy Korean subjects. METHODS:A single 5-mg capsule of tropisetron was administered orally to 13 healthy subjects. Plasma concentrations were determined by validated HPLC procedures and data were analyzed by using nonc...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-003-0595-1
更新日期：2003-06-01 00:00:00
abstract：:We have evaluated the effects of repaglinide, a new non-sulphonylurea oral hypoglycaemic agent that has a stimulatory effect on insulin secretion. Forty-four patients with NIDDM, already treated with a sulphonylurea, took part in an open, randomised, group comparison study of 12 weeks duration, during which they recei...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00315490
更新日期：1993-01-01 00:00:00
abstract：PURPOSE:The objective of this study was to appraise the safety profiles of HES preparations and to find out which HES preparation was the most acceptable in cardiovascular surgery through a comparison with control solutions. METHODS:Pertinent randomized controlled trials were selected through a search of Pubmed, Embas...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,meta分析,评审
doi：10.1007/s00228-011-1008-5
更新日期：2011-08-01 00:00:00
abstract：:We have shown that apparent nonlinearities in the pharmacokinetics of chloroquine and wide variability in reported kinetic values are possibly artefacts of experimental design. We have used simulated data based on linear equations to demonstrate that chloroquine kinetics may appear to be dose-dependent if samples are ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00541305
更新日期：1987-01-01 00:00:00
abstract：OBJECTIVE:To describe trends in opioid consumption in Israel (morphine, methadone, oxycodone, pethidine, fentanyl, buprenorphine, codeine, and dextropropoxyphene) over the 9 years, 2000-2008, and to explore explanations for changes in consumption, in amounts and the pattern. METHODS:Data for the 2000-2008 period (all ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-010-0932-0
更新日期：2011-02-01 00:00:00
abstract：OBJECTIVE:To investigate (1) the pharmacokinetic and pharmacodynamic profiles of desmopressin in men from an age group with a high incidence of nocturia; and (2) circadian variation in the pharmacokinetic parameters. METHODS:The study had an open, randomised, four-way cross-over design. Desmopressin was administered o...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/s00228-004-0781-9
更新日期：2004-08-01 00:00:00
abstract：OBJECTIVE:To investigate the CYP1A2 phenotype distribution in a population with an increased exposure to polychlorinated biphenyls (PCBs) that would likely induce an increased activity of this enzyme. Further, to investigate the effect of sex, smoking, and oral contraceptive use on the CYP1A2 activity. METHODS:In 305 ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-006-0205-0
更新日期：2006-12-01 00:00:00
abstract：:One hundred consecutive digitalis serum level determination requests and results were analyzed to evaluate the rational of ordering the test and utilizing the results at his hospital. Sixty-six percent of the reasons given for ordering the test were categorized as "acceptable". As many as 25% of physicians requesting ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00561740
更新日期：1979-07-01 00:00:00
abstract：:Four subjects received 5 mg 14C-glipizide orally, 3 subjects 1 mg intravenously and 2 subjects 5 mg 14C-glibenclamide orally. Plasma levels of radioactivity, and urinary and faecal excretion were measured. For both drugs the disappearance of radioactivity from plasma followed complex kinetics and the apparent half-liv...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00616416
更新日期：1975-01-01 00:00:00
abstract：BACKGROUND:Maintenance of the structural and functional integrity of the skeleton is a critical function of a continuous remodeling driven by highly associated processes of bone resorption and synthetic activities driven by osteoclasts and osteoblasts, respectively. Acceleration of bone turnover, accompanied with a dis...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-006-0174-3
更新日期：2006-10-01 00:00:00
abstract：:The pharmacokinetics of piretanide, a new loop diuretic, were studied in seven patients with severe liver disease before and after resolution of ascites. The time to maximum concentration was significantly prolonged by the presence of ascites. Tmax after relief of ascites was similar to that seen for normal volunteers...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00544070
更新日期：1985-01-01 00:00:00
abstract：:A questionnaire survey was carried out to explore differences in the approach to treatment of patients with Type II diabetes between physicians in Northern Ireland, Norway and Sweden, and to discover to what extent it could account for the three-fold difference in drug use between the countries. A representative sampl...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542408
更新日期：1986-01-01 00:00:00
abstract：:An analytical procedure for the simultaneous determination of pethidine and its N-Demethylated metabolite, norpethidine, in plasma is described. Pethidine and norpethidine are separated by partition chromatography, converted to the trichloroethyl carbamate with trichloroethyl chloroformate and determined by electron c...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00561790
更新日期：1977-01-01 00:00:00
abstract：OBJECTIVES:To compare plasma levodopa concentrations after repeated doses of levodopa/carbidopa/entacapone (LCE) and levodopa/carbidopa (LC). METHODS:Open-label, randomized, two-period, active-controlled, cross-over study with four dosing regimens: groups I and II (healthy volunteers and Parkinson's disease patients) ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-009-0622-y
更新日期：2009-05-01 00:00:00
abstract：:Eighty patients recovering from major operations were investigated to evaluate the influence of naloxone on the analgesic and respiratory depressant properties of buprenorphine. They were randomly assigned to two groups to self-administer either buprenorphine (Group B) or a mixture of buprenorphine and naloxone (fract...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00542434
更新日期：1988-01-01 00:00:00
abstract：BACKGROUND:Serious adverse effects have been observed with some non-sedative H1-antihistamines (terfenadine and astemizole) when they were associated with drugs known to inhibit their metabolism. However, this is not a class effect, and this interaction should be considered on a case-by-case basis. The aim of this stud...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-005-0917-6
更新日期：2005-06-01 00:00:00
abstract：OBJECTIVE:To investigate the influence of concomitant administration of roxithromycin on the plasma pharmacokinetics of lovastatin. METHODS:In an open, randomized, crossover study, 12 healthy volunteers received 80 mg lovastatin orally either alone or concomitantly with 300 mg roxithromycin after 5-day pretreatment wi...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/s00228-001-0385-6
更新日期：2002-01-01 00:00:00
abstract：:The effect of dexfenfluramine (dF) on body weight, blood pressure and noradrenergic activity were studied in 30 obese hypertensive patients randomly divided into two groups and treated for 3 months either with dF (30 mg daily; 16 subjects) or placebo (Pl; 14 subjects). 11 patients from the dF group and 9 patients give...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00265922
更新日期：1992-01-01 00:00:00
abstract：OBJECTIVE:To determine the pharmacokinetics and organ distribution of i.v. and oral methylene blue, which is used to prevent ifosfamide-induced encephalopathy in oncology. METHODS:The concentration of methylene blue in whole blood was measured using high-performance liquid chromatography in seven volunteers after i.v....
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280000124
更新日期：2000-06-01 00:00:00
abstract：:In this paper an alternative approach to nonlinear pharmacokinetics modelling has been developed from first principles. This "Unsteady Model" is able to describe the situation whereby one or more independent drugs and their metabolites compete for free attachment sites in liver, tissue, red blood cells etc. The Unstea...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00615410
更新日期：1981-01-01 00:00:00
abstract：:A new acid thiol, 2-mercaptopropionate, has been identified by GC-MS in urine from cystinuric patients on treatment with 2-mercaptopropionylglycine. The amount excreted was 50-300 mumol/24h and it was correlated with the oral dose of 2-mercaptopropionyl-glycine. The observation may be of clinical importance as the met...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00871000
更新日期：1986-01-01 00:00:00
abstract：AIM:The investigations reported here aimed to evaluate the incremental benefit for dose finding by concentration-response analysis versus dose-response analysis. METHODS:Trials were simulated using an Emax model for a range of scenarios of drug properties, trial design options and target response levels. The simulated...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-013-1474-z
更新日期：2013-07-01 00:00:00
abstract：INTRODUCTION:This study compared the characteristics of new human drugs approved by the Food and Drug Administration (FDA), the European Medicine Agency (EMA), and Swissmedic (SMC) in the period 2007 to 2016. METHODS:The list of new drugs and therapeutic biologics approved by the FDA, the EMA, and SMC in the period 20...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-018-2431-7
更新日期：2018-06-01 00:00:00
abstract：OBJECTIVE:To investigate whether an association between the use of selective serotonin reuptake inhibitor (SSRI) antidepressants and abnormal bleeding is demonstrated in a large population study. METHODS:An observational cohort study using cohorts from the Drug Safety Research Unit's prescription event monitoring data...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280100263
更新日期：2001-05-01 00:00:00
abstract：OBJECTIVE:A double-blind, placebo-controlled parallel study was conducted on the effect of mibefradil, both an L- and T-type Ca2+-channel blocker with a more selective blockade of T-type channels, administered once daily for 1 week to normal male subjects, on blood pressure, intracellular cationic concentrations, sodiu...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/s002280050574
更新日期：1999-02-01 00:00:00
abstract：:Six children, aged 2 months - 4 years, received theophylline 5-6 mg/kg intravenously. Its disposition could be described by a two-compartment open model, the mean serum half life (t 1/2 beta) was 3.75 h, i.e., shorter than in adults, but there was a considerable interindividual variation (1.8-7.0 h, in one patient 13....
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00563120
更新日期：1979-09-01 00:00:00
abstract：OBJECTIVE:The primary objective was to evaluate the effect of 7 days treatment with nimesulide on bleeding time. Blood coagulation, von Willebrand factor and platelet aggregation ex vivo were investigated as a secondary objective. METHOD:A randomised, double-blind, placebo-controlled, parallel group, single centre stu...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/s002280050479
更新日期：1998-07-01 00:00:00
abstract：:The binding of ibuprofen to human serum albumin, normal plasma and plasma obtained from rheumatoid arthritic patients was studied using the method of ultracentrifugation. It was found that ibuprofen is more strongly bound to normal plasma than to human serum albumin although this result is probably explained by fatty ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542526
更新日期：1983-01-01 00:00:00
abstract：PURPOSE:Tacrolimus is a commonly used immunosuppressant in solid organ transplantation recipients, but it is characterized by a narrow therapeutic range and large inter-individual variability. The purpose of this study was to establish a population pharmacokinetic (PK) model of tacrolimus and evaluate the influence of ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-012-1296-4
更新日期：2013-01-01 00:00:00
