Warfarin is an anticoagulant drug with narrow therapeutic index and high interindividual variability in dose requirement. S-warfarin is metabolized mainly by polymorphic cytochrome P450 (CYP) 2C9. We systematically quantified the influence of CYP2C9 genotype, demographic factors and concomitant drug treatment on warfarin metabolism and maintenance dose. The mean warfarin doses were lower in carriers of one (2.71 mg/day, 59 patients) and two polymorphic alleles (1.64 mg/day, 11 patients) than in carriers of two wild-type alleles (4.88 mg/day, 118 patients). Multiple regression analysis demonstrated that CYP2C9 genotype, age, concomitant treatment with warfarin metabolism inducers and lean body weight contributed significantly to interindividual variability in warfarin dose requirement (adjusted R 2 ¼ 0.37). The same factors, except for age, significantly influenced S-warfarin clearance (adjusted R 2 ¼ 0.42). These results can serve as a starting point for designing prospective studies in patients in the initiation phase of genotype-based warfarin therapy.

The deficiency of clinical relevance of detected DDIs should be addressed in the upcoming research as it would provide more relevant information to the prescribers' in clinical practice.

Among second-generation antipsychotics, which have a better safety profile than first-generation antipsychotics, olanzapine and risperidone showed to be the most cost-effective treatment strategies for outpatient treatment of chronic schizophrenia.

No abstract

Genotyping in combination with a subsequent reduction of initial irinotecan dose for UGT1A1 7/7 genotype patients was cost-saving for the population of African and Caucasian origin. By contrast, UGT1A1 genotyping was not cost effective for the population of Asian ancestry. Furthermore, the prophylactic use of G-CSFs in UGT1A1 7/7 genotype patients was not cost effective in any population group. Finally, the application of a 3-weekly high-dose treatment regimen with a 20% reduced dosage compared with the low-dose weekly irinotecan regimen in patients with UGT1A1 7/7 genotype was less expensive and is more convenient for the patient.

AimsPharmacokinetic (PK) studies suggest that there is a room for improvement in clinical use of rituximab through more individualized treatment. The objective of this study was to characterize rituximab PK in 29 newly diagnosed patients with diffuse large B‐cell lymphoma treated with rituximab in combination with cyclophosphamide, doxorubicin, vincristine and methylprednisolone every 3 weeks. We also evaluated the association of rituximab PK with clinical outcome.MethodsRituximab serum levels were determined by enzyme‐linked immunosorbent assay and evaluated by a population PK analysis applying nonlinear mixed effects modelling.ResultsThe data were best described by a two‐compartment model comprising linear nonspecific clearance of 0.252 [95% confidence interval (CI): 0.227–0.279] l day–1 and time‐varying specific clearance of 0.278 (95% CI: 0.181–0.390) l day–1, corresponding to target‐mediated drug disposition of rituximab. Nonspecific clearance was lower in older patients and those with lower body weight. Additionally, volume of the central compartment was higher in males. A clear association of clinical response with rituximab PK has been observed. Rate constant of specific clearance decay was 0.143 day−1 (95% CI: 0.0478–0.418) in patients with no disease progression, while in patients with disease progression it was 82.2% lower (95% CI: 33.4–95.0).ConclusionsThis finding indicates that time‐changes in clearance could serve as a predictive marker of response to rituximab. Our report demonstrates the rationale for studies evaluating higher doses of rituximab in selected patients.

Mental health problems (MHPs) are very common in the elderly and can have an important influence on their quality of life (QoL). There is almost no data on the impact of clinical pharmacists’ (CPs) interventions on the QoL including elderly patients and MHPs. The main aim of this study was to determinate the impact of (CP’s) interventions on the QoL and quality of pharmacotherapy. A prospective non-randomized pre-post study was designed which included residents of a nursing home aged 65 age or more with at least one MHP. Each patient also filled out the EQ-5D questionnaire. The medical review MR included drug-related problems (DRPs) and potentially drug-drug interactions (pDDIs), as well as potentially inappropriate medications (PIMs). After 2 months, the participants were interviewed again. The mean number of medications before the intervention was 12,2 ± 3,1 per patient and decreased to 10,3 ± 3,0 medications per patient (p < 0,05) (n = 24). The total number of PIMs and pDDIs was also reduced and QoL was also significantly higher (p < 0,05). A collaborative care approach with a CP led to a decrease of DRPs, pDDIs, PIMs, the total number of medications and to an improvement in the patients’ QoL.

This study assessed the effects of statins on preventing clinical events associated with cardiovascular disease (CVD). The authors concluded that there was a considerable reduction in risk of CVD morbidity and mortality in people with CVD, and a small reduction in risk in those without CVD. Searching MEDLINE was searched from 1985 to July 2002; the search terms were given. In addition, the Cochrane Library was searched and the reference lists of identified studies and reviews were checked. The authors also implied that they searched Ringdoc. Only studies in English, German, French or Italian were eligible for inclusion. Study selection Study designs of evaluations included in the review Only randomised placebo-controlled trials, with more than 30 participants with hypercholesterolaemia per group, were eligible for inclusion. Specific interventions included in the review Only studies of statins compared with placebo were eligible for inclusion. The duration of treatment had to be one year or more. The statins used in the included studies were simvastin, pravastatin or lovastatin. The treatments ranged from 1 to 6.1 years in duration. In one of the included studies some of the participants also received antioxidant vitamins. Participants included in the review The inclusion criteria stated that studies on people with no evidence of cardiovascular disease (CVD) (primary prevention), or on those with CVD (secondary prevention), were eligible for inclusion. In one included study some participants had CVD whilst others did not (mixed primary and secondary prevention). In the included studies, the majority of the participants were male (52 to 100%) and the mean ages ranged from 53 to 62 years. Some participants had hypertension, diabetes, angina or myocardial infarction, or were smokers. Outcomes assessed in the review Only primary and secondary prevention studies with clinical outcomes (i.e. CHD mortality, all-cause mortality, stroke, stroke mortality, coronary disease event) were eligible for inclusion. The results were grouped by treatment objective (primary, secondary, or combined or mixed studies). Changes in cholesterol levels were also reported: total cholesterol, low-and high-density lipoprotein cholesterol (LDL and HDL, respectively) and triglycerides. How were decisions on the relevance of primary studies made? Two authors independently selected papers for inclusion. Assessment of study quality The authors did not state that they assessed validity.