Development of clinical pharmacology as a medical speciality in Europe - the roles of WHO, IUPHAR and EACPT.

This MiniReview shows that both WHO and IUPHAR very early recognized that there is a gap between the availability of academic expert knowledge in pharmacology and its utilization in health care. Many initiatives have been taken to bridge this gap, but still 12 European countries do not recognize clinical pharmacology as a medical speciality because the profession has failed to develop defined functions in patient care. A first priority for EACPT therefore ought to be to promote clinical pharmacology as a medical speciality recognized by the European Union.

Clinical Pharmacology in European health care-outcome of a questionnaire study in 31 countries.

Introduction: In order to discover how well the discipline of clinical pharmacology (CP) has developed in Europe, a questionnaire survey was undertaken in 31 countries.

Methods: The senior delegate of each of the 31 countries on the Council of the European Association for Clinical Pharmacology and Therapeutics (EACPT) was approached personally. This study was not an official EACPT survey.

The 'wise list'- a comprehensive concept to select, communicate and achieve adherence to recommendations of essential drugs in ambulatory care in Stockholm.

The aim was to present and evaluate the impact of a comprehensive strategy over 10 years to select, communicate and achieve adherence to essential drug recommendations (EDR) in ambulatory care in a metropolitan healthcare region. EDRs were issued and launched as a 'Wise List' by the regional Drug and Therapeutics Committee in Stockholm. This study presents the concept by: (i) documenting the process for selecting, communicating and monitoring the impact of the 'Wise List'; (ii) analysing the variation in the number of drug substances recommended between 2000 and 2010; (iii) assessing the attitudes to the 'Wise List' among prescribers and the public; (iv) evaluating the adherence to recommendations between 2003 and 2009.

Use of doping agents, particularly anabolic steroids, in sports and society.

The use of doping agents, particularly anabolic androgenic steroids (AAS), has changed from being a problem restricted to sports to one of public-health concern. We review the prevalence of misuse, the evidence that some drugs improve performance in sport, their side-effects, and the long-term consequences of AAS misuse for society at large. There is substantial under-reporting of the side-effects of AAS to health authorities.

Depot haloperidol treatment in outpatients with schizophrenia on monotherapy: impact of CYP2D6 polymorphism on pharmacokinetics and treatment outcome.

Haloperidol and several other antipsychotic drugs are at least partially metabolized by the polymorphic cytochrome P450 2D6 (CYP2D6). The interindividual variation in metabolic capacity of CYP2D6 might be of importance when dosing. In this study, 26 outpatients with schizophrenia and depot haloperidol as monotherapy were genotyped.

The convergence of conventional therapeutic drug monitoring and pharmacogenetic testing in personalized medicine: focus on antidepressants.

The development and prospects of conventional therapeutic drug monitoring (TDM) and pharmacogenetic testing as aids in personalized treatment with antidepressants and antipsychotics are described. Our own experience is discussed in relation to international guidelines for rational TDM. Emphasis is put on the usefulness of TDM combined with genotyping of cytochrome P450 2D6 (CYP2D6), the key enzyme involved in the polymorphic metabolism of the majority of antidepressants (both tricyclics and selective serotonin reuptake inhibitors) and antipsychotic drugs.

Merck fellowships contribute to the continued growth of clinical pharmacology in Sweden.

Since 1990, Merck, Sharpe & Dohme, Sweden, has created fellowships for physicians embarking upon a career in clinical pharmacology at Swedish medical schools. The fellowship has provided full salary at the level of a resident in clinical medicine for an average period of 1-2 years. Between 1992 and 2004, 22 fellows representing all six medical schools were selected for a fellowship.

Therapeutic monitoring of antiepileptic drugs: a comparison between a Czech and a Swedish University Hospital.

Plasma concentrations obtained during routine therapeutic monitoring of antiepileptic drugs (AED) (N03A ATC group) were compared in patients treated with one or several AED in the University Hospitals in Ostrava, Czech Republic and Huddinge, Sweden. Request and reply forms for therapeutic drug monitoring (TDM) were used as a source of mean plasma concentrations (PC). The study included 2,824 adult out- and inpatients in Huddinge treated from 1995 to 1999 and 1,268 outpatients treated in Ostrava from 1993 to 2004.

The use of TDM data to assess the validity of defined daily doses of antiepileptics: a comparison between a Czech and Swedish University Hospital.

Prescribed daily doses (PDDs) of antiepileptic drugs (AED) (N03A ATC group) were recorded for drugs used in monotherapy or in combination therapy in the University Hospitals in Ostrava, Czech Republic and Huddinge, Sweden. Plasma concentrations were used as an indicator of the quality of treatment. PDDs were compared with the defined daily doses (DDDs) suggested by WHO in the ATC/DDD index 2005.

The anti-doping hot-line, a means to capture the abuse of doping agents in the Swedish society and a new service function in clinical pharmacology.

With the support of the Swedish National Institute of Health a national information service was started in 1993 aiming to capture the abuse of doping agents in the general public. It was organized as a telephone service, called the Anti-Doping Hot-Line, from our department and managed by trained nurses co-operating with clinical pharmacologists. Important information collected about all callers (anonymous) was: date of call, its origin, category of caller, doping experience and main question being asked.

The role of CYP2C9 genotype in the metabolism of diclofenac in vivo and in vitro.

Introduction: The polymorphic cytochrome P450 enzyme 2C9 (CYP2C9) catalyses the metabolism of many drugs including S-warfarin, acenocoumarol, phenytoin, tolbutamide, losartan and most of the non-steroidal anti-inflammatory drugs. Diclofenac is metabolised to 4'-hydroxy (OH), the major diclofenac metabolite, 3'-OH and 3'-OH-4'-methoxy metabolites by CYP2C9. The aim of the present study was to clarify the impact of the CYP2C9 polymorphism on the metabolism of diclofenac both in vivo and in vitro.

Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype.

Background And Aim: Losartan is metabolized by polymorphic CYP2C9 to E-3174. Our aim was to evaluate the pharmacokinetics of losartan and E-3174 in relation to the CYP2C9 genotype.

Methods: A 50-mg oral dose of losartan was given to 22 Swedish volunteers with different CYP2C9 genotypes.

[Quality assurance of drug prescription in primary health care. A new database software makes the drug therapy surveillance easier].

Quality assurance of drug prescription is a pre-requisite for rational drug use. From 22 health-care centres in the south-western area of the Stockholm County Council region, drug-prescription data were obtained from the patients' computerised medical recordings. This could be done with the aid of a specially designed database program.

Correlation of gene expression of ten drug efflux proteins of the ATP-binding cassette transporter family in normal human jejunum and in human intestinal epithelial Caco-2 cell monolayers.

This investigation describes the expression and interindividual variability in transcript levels of multiple drug efflux systems in the human jejunum and compares the expression profiles in these cells with that of the commonly used Caco-2 cell drug absorption model. Transcript levels of ten-drug efflux proteins of the ATP-binding cassette (ABC) transporter family [MDR1, MDR3, ABCB5, MRP1-6, and breast cancer resistance protein (BCRP)], lung resistance-related protein (LRP), and CYP3A4 were determined using quantitative polymerase chain reaction in jejunal biopsies from 13 healthy human subjects and in Caco-2 cells. All genes except ABCB5 were expressed, and transcript levels varied between individuals only by a factor of 2 to 3.

CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages.

Objective: This review aimed to provide distinct dose recommendations for antidepressants based on the genotypes of cytochrome P450 enzymes CYP2D6 and CYP2C19. This approach may be a useful complementation to clinical monitoring and therapeutic drug monitoring.

Method: Our literature search covered 32 antidepressants marketed in Europe, Canada, and the United States.