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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. The 'Wise List' consistently contained 200 drug substances for treating common diseases. The drugs were selected based on their efficacy, safety, suitability and cost-effectiveness. The 'Wise List' was known among one-third of a surveyed sample of the public in 2002 after initial marketing campaigns. All surveyed prescribers knew about the concept and 81% found the recommendations trustworthy in 2005. Adherence to recommendations increased from 69% in 1999 to 77% in 2009. In primary care, adherence increased from 83% to 87% from 2003 to 2009. The coefficient of variation (CV%) decreased from 6.1% to 3.8% for 156 healthcare centres between these years. The acceptance of the 'Wise List' in terms of trust among physicians and among the public and increased adherence may be explained by clear criteria for drug recommendations, a comprehensive communication strategy, electronic access to recommendations, continuous medical education and involvement of professional networks and patients.

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 authors found 1 patient with no functional alleles, 8 with one functional allele, 16 with two functional alleles, and 1 with three functional alleles. The daily dose of haloperidol ranged from 0.45 to 14.29 mg. Steady state plasma concentrations were measured at peak (range, 1.6-67 nmol/L) and at trough (range, 1.0-49 nmol/L). The Positive and Negative Syndrome scale for Schizophrenia and the Extrapyramidal Symptom Rating Scale were used to evaluate the clinical effect. The authors found a clear correlation between haloperidol plasma concentration and number of active CYP2D6 alleles. No correlation was found between plasma concentration of haloperidol or number of CYP2D6 alleles and treatment outcome or side effects. A model to predict plasma concentration from dose and number of active CYP2D6 alleles was formed from the obtained data by means of multiple linear regression.

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. Surprisingly, BCRP and MRP2 transcripts were more abundant in jejunum than MDR1 transcripts. Jejunal transcript levels of the different ABC transporters spanned a range of three log units with the rank order: BCRP approximately MRP2 > MDR1 approximately MRP3 approximately MRP6 approximately MRP5 approximately MRP1 > MRP4 > MDR3. Furthermore, transcript levels of 9 of 10 ABC transporters correlated well between jejunum and Caco-2 cells (r2 = 0.90). However, BCRP exhibited a 100-fold lower transcript level in Caco-2 cells compared with jejunum. Thus, the expression of a number of efflux protein transcripts in jejunum are equal to, or even higher than, that of MDR1, suggesting that the roles of these proteins (in particular BCRP and MRP2) in intestinal drug efflux have been underestimated. Also, we tentatively conclude that the Caco-2 cell line is a useful model of jejunal drug efflux, if the low expression of BCRP is taken into account.