Amphotericin B remains a very important drug for the treatment of fungal infections despite its toxicity. Encapsulation of amphotericin B into liposomes appears to reduce the toxic effects and to improve the clinical efficacy, allowing higher dosages to be given. The exact mechanism behind the reduced toxicity is not yet known. Amphotericin B is widely distributed after intravenous administration as the deoxycholate solubilisate. The highest concentrations are found in the liver, spleen and kidney. Protein binding and binding to the tissues is very high. The fate of the drug in the body is not known in detail. Renal and biliary excretion are both low and no metabolites have been identified. The drug is still detectable in the liver, spleen and kidney for as long as 1 year after stopping therapy. The pharmacokinetics of the different liposomal amphotericin B or lipid complexes of amphotericin B, which were recently developed, are quite diverse. A number of these preparations, such as amphotericin B lipid complex (ABLC), 'AmBisome' and amphotericin B colloidal dispersion (ABCD) are in clinical development. Their pharmacokinetics depend to a large extent on the composition and particle size of the liposomes or lipid complexes. Relatively large structures such as ABLC are rapidly taken up by the mononuclear phagocyte system, whereas smaller liposomes remain in the circulation for prolonged periods. In all studies only the total amphotericin B (both free and liposome- or lipid-associated) concentrations were determined. There is a need for studies correlating clinical efficacy and tolerability of liposomal amphotericin B with the pharmacokinetic properties of these formulations.

It is important for diabetic patients using antidepressants for more than 3 years to pay attention for symptoms of hypoglycaemia and strict blood glucose self-monitoring.

Antidepressants have different receptor binding profiles, which are related to therapeutic action and adverse drug reactions. We constructed a model to classify antidepressants on the basis of their binding properties of most common transporter-and receptor sites. Receptor binding was quantified by calculating receptor occupancy for the 5-HT (serotonin) reuptake transporter, norepinephrinic reuptake transporter, 5-HT 2C -receptor, M 3 -receptor, H 1 -receptor and 1 -receptor. To identify groups of antidepressants that show similar patterns of receptor occupancy for different receptors, hierarchical cluster analysis (HCA) and principle component analysis (PCA) were used. In addition, to visualize (a)symmetry between binding profiles of antidepressants, radar plots were constructed. On the basis of both analyses, four clusters of antidepressants which exert similar pharmacological properties were identified. Potentially, this model could be a helpful tool in medical practice and may be used as a prediction model for adverse effects of drugs entering the market.

Objectives Depression is common in patients with diabetes, and the use of antidepressants may impair glycaemic control. We assessed the association between antidepressant use and hyper-and hypoglycaemia. Methods Based on spontaneous reports listed in the World Health Organization (WHO) Adverse Drug Reaction Database, a case-control study was conducted. The study base consisted of all adverse drug reactions (ADRs) ascribed to antidepressants, antipsychotics and benzodiazepines between 1969 and 2005. Cases were defined as reported ADRs classified as hyper-or hypoglycaemia and separated in different study populations. All other reports were considered as controls. Exposure to antidepressants was the primary determinant investigated. Benzodiazepines and antipsychotics were chosen as reference groups. Potential confounding factors, namely, age, gender, use of antidiabetic medication, use of hyper-or hypoglycaemiainducing comedication and reporting year, were determined on the index date. Multivariate logistic regression was used to evaluate the strength of the association, which was expressed as reporting odds ratios (RORs) with 95% confidence intervals (95% CI). Results Overall, the use of antidepressants was associated with hyperglycaemia [ROR 1.52 (95% CI: 1.20-1.93)] and of hypoglycaemia [ROR 1.84 (95% CI: 1.40-2.42)]. The association with hyperglycaemia was most pronounced for antidepressants with affinity for the 5-HT 2c receptor, histamine-1 receptor and norepinephrinic (NE) reuptake transporter. The association with hypoglycaemia was most pronounced for antidepressants with affinity for the serotonin reuptake transporter. Conclusion The results of this study strengthen the findings in individual case reports that the use of antidepressants is associated with disturbances in glucose homeostasis.

The use of antibiotics in Dutch hospitals between 1991 and 1996 was investigated. A total of 54 hospitals responded to the enquiry, representing over 70% of all hospital beds in The Netherlands. The use of antibiotics in Dutch hospitals, expressed as defined daily doses (DDD) per hundred bed days, gradually increased from 37.2 DDD per 100 bed days in 1991 to 42.5 DDD per 100 bed days in 1996. The antibiotic that showed the largest increase in use was co-amoxiclav. Its use increased more than three-fold from 3.93 DDD per 100 bed days in 1991 to 12.5 DDD per 100 bed days in 1996. The increase in use of co-amoxiclav exceeded the increase in total antibiotic consumption. The use of cephalosporins remained fairly constant during the study period, but there were changes in the relative use of the different cephalosporin groups. The use of earlier cephalosporins gradually decreased, whereas the use of the more recently developed cephalosporins increased between 1991 and 1996. Ciprofloxacin and norfloxacin were the most commonly used fluoroquinolones throughout the study period. The use of ofloxacin increased significantly between 1991 and 1996, approaching the levels of use of ciprofloxacin and norfloxacin. There may be complex reasons for the increases, which need further analysis, but they mirror those few data available from elsewhere in the world. Possible explanations include more intensive treatment to expedite patient discharges, sicker patients with more serious infections and more resistant organisms.

Drug selection of rapid acting fentanyl formulations in the treatment of breakthrough pain in patients with cancer is performed by the System of Objectified Judgement Analysis method. All seven available formulations were included in the analysis. The following selection criteria were used: number of available strengths, variability in the rate of absorption, interactions, clinical efficacy, side effects, ease of administration and documentation. No direct double-blind comparative studies between two or more formulations were identified and the clinical documentation of all formulations is limited. The most distinguishing criterion was ease of use. This led to slightly higher scores for Abstral, Instanyl and PecFent than for the other formulations. The pros and cons of each formulation should be discussed with the patient, and the most suitable formulation selected for each individual patient.

Drug selection should be a rational process that embraces the principles of evidence-based medicine. However, many factors may affect the choice of agent. It is against this background that the System of Objectified Judgement Analysis (SOJA) process for rational drug-selection was developed. This article describes how the information on which the SOJA process is based, was researched and processed.

Data on the use of antimicrobial drugs was collected by means of an inquiry to 30 hospitals in Belgium (15 in Dutch sectors and 15 in the French sectors), 21 hospitals in Germany and 20 hospitals in the Netherlands. The use of these drugs was expressed as the number of defined daily doses (DDD) per 100 bed days by the anatomical therapeutical chemical classification system. The total use of antimicrobial agents was significantly (p < 0.001) higher in both parts of Belgium (55.6 and 52.0 DDD per 100 bed days) than in Germany (37.9 DDD) or the Netherlands (34.1 DDD). In particular, amoxicillin-clavulanic acid, the first- and second-generation cephalosporins, aminoglycosides and fluoroquinolones were used more in Belgium than in either of the other countries. At least part of the differences observed in antimicrobial drug use could be explained by differences in written antibiotic policy.