Administration of rhACE2 was well tolerated by healthy human subjects. Exposure was dose dependent with a dose-independent terminal elimination half-life in the range of 10 h. Despite marked changes in angiotensin system peptide concentrations, cardiovascular effects were absent, suggesting the presence of effective compensatory mechanisms in healthy volunteers.

Problems associated with pharmacotherapy (in particular, medication errors and adverse drug events) are frequent and are associated with increased costs for treatment. Analysis of original publications published between 1990 and 2005 on the topics of medication errors and/or adverse drug events in hospitalised patients, focusing on the frequency of, risk factors for and avoidance of such problems associated with pharmacotherapy, indicated that medication errors occurred in a mean of 5.7% of all episodes of drug administration, but with a high variability among the 35 studies retrieved. This variability was explained by the methods by which medication errors were detected (systematic screening of patients versus chart review or spontaneous reporting) and by the way drugs were administered (intravenously administered drugs are associated with the highest error frequencies). Errors occurred throughout the whole medication process, with administration errors accounting for more than half of all errors. Important risk factors included insufficient pharmacological knowledge of health professionals, errors in the patient charts or documentation by nurses and inadequate pharmacy services.Adverse events or reactions, on the other hand, affected 6.1 patients per 100 hospitalised and also showed a high variability among the 46 studies retrieved. This variability could also be explained by the different methods of assessment of the frequency of adverse drug events or reactions, as well as by the different wards on which the studies were performed. Important risk factors for adverse drug events or reactions included polypharmacy, female sex, drugs with a narrow therapeutic range, renal elimination of drugs, age >65 years and use of anticoagulants or diuretics. Since medication errors are strong risk factors for preventable adverse drug events or reactions, strategies have to be put in place for their reduction. Such strategies include ensuring that all persons involved in the medication process (nurses, pharmacists and physicians) have good pharmacological knowledge, computerisation of the entire medication process, and the engagement of a sufficient number of clinical pharmacists on the wards.

Limited treatment options are available for implant-associated infections caused by methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). We compared the activity of daptomycin (alone and with rifampin [rifampicin]) with the activities of other antimicrobial regimens against MRSA ATCC 43300 in the guinea pig foreign-body infection model. The daptomycin MIC and the minimum bactericidal concentration in logarithmic phase and stationary growth phase of MRSA were 0.625, 0.625, and 20 g/ml, respectively. In time-kill studies, daptomycin showed rapid and concentration-dependent killing of MRSA in stationary growth phase. At concentrations above 20 g/ml, daptomycin reduced the counts by >3 log 10 CFU/ml in 2 to 4 h. In sterile cage fluid, daptomycin peak concentrations of 23.1, 46.3, and 53.7 g/ml were reached 4 to 6 h after the administration of single intraperitoneal doses of 20, 30, and 40 mg/kg of body weight, respectively. In treatment studies, daptomycin alone reduced the planktonic MRSA counts by 0.3 log 10 CFU/ml, whereas in combination with rifampin, a reduction in the counts of >6 log 10 CFU/ml was observed. Vancomycin and daptomycin (at both doses) were unable to cure any cage-associated infection when they were given as monotherapy, whereas rifampin alone cured the infections in 33% of the cages. In combination with rifampin, daptomycin showed cure rates of 25% (at 20 mg/kg) and 67% (at 30 mg/kg), vancomycin showed a cure rate of 8%, linezolid showed a cure rate of 0%, and levofloxacin showed a cure rate of 58%. In addition, daptomycin at a high dose (30 mg/kg) completely prevented the emergence of rifampin resistance in planktonic and adherent MRSA cells. Daptomycin at a high dose, corresponding to 6 mg/kg in humans, in combination with rifampin showed the highest activity against planktonic and adherent MRSA. Daptomycin plus rifampin is a promising treatment option for implant-associated MRSA infections.

This new combination of phenotyping probe drugs can be used without mutual interactions. The proposed sampling timepoints have the potential to facilitate clinical application of phenotyping but require further validation in conditions of altered CYP activity. The use of DBS or saliva samples seems feasible for phenotyping of the selected CYP isoforms.