Assessment of the environmental fate and effects of azilsartan, a selective antagonist of angiotensin II type 1.

In this paper the results of a thorough evaluation of the environmental fate and effects of azilsartan are presented. Azilsartan medoxomil is administered as a pro-drug for the treatment of patients with essential hypertension. The pro-drug is converted by hydrolysis to the active pharmaceutical ingredient azilsartan. Laboratory tests to evaluate the environmental fate and effects of azilsartan medoxomil were conducted with azilsartan and performed in accordance with OECD test guidelines. The predicted environmental concentration (PEC) in surface water was estimated at 0.32 µg L(-1) (above the action limit of 0.01 µg L(-1)), triggering a Phase II assessment. Azilsartan is not readily biodegradable. Results of the water sediment study demonstrated significant shifting of azilsartan metabolites to sediment. Based on the equilibrium partitioning method, metabolites are unlikely to pose a risk to sediment-dwelling organisms. Ratios of the predicted environmental concentrations (PECs) to the predicted-no-effect concentrations (PNECs) did not exceed the relevant triggers, and the risk to aquatic, sewage treatment plant (STP), groundwater and sediment compartments was concluded acceptable. A terrestrial assessment was not triggered. Azilsartan poses an acceptable risk to the environment.

Improvement of patient education and information: development of a patient's information dossier.

The demand for patient information in modern medical care is increasing and sound information for patients is becoming a necessity. For haemophilia patients, information about their disease and its complications is already widely available. In order to increase the organization of this information, a 'Patient Information Dossier' (PID) and communication check lists were developed at the Dutch National Hemophilia Center, the Van Creveldkliniek, in cooperation with the Department of Patient Education of the University Medical Center Utrecht. The PID has an unique double function: (1) it contains patient tailored information about the practical facts of hospital care; and (2) it provides a communication checklist used by various members of the comprehensive care team, in order to supply patients with more uniform information. In order to gain a better insight of the gaps in information supply, according to patients and healthcare workers, the Department of Patient Education formulated a questionnaire. The PID itself was written by a study group consisting of members of the comprehensive care team. The entire process was developed, edited and coordinated by an advisor of the Department of Patient Education. The above-mentioned study group developed a specific PID on haemophilia care. Its 10 chapters provide information and guidelines, and advise patients where to find more information about this subject. Each chapter includes a checklist for patients, enabling them to prepare subjects for discussion during clinical visits. The team also developed a communication checklist to be used by various team members during a patient's visit to the clinic, as well as specific checklists covering the possible problem subjects of the PID. The PID is the lifelong property of the patient, and can be used during each visit to the clinic. The PID was implemented in February 2000, and within 4 months, was distributed among 200 patients visiting the Van Creveldkliniek. Evaluation by use of a questionnaire showed that most patients found the information in the PID sufficient and in accordance with that which they had received previously.

Development of a bioassay to test the possible role of thiamine disturbance as a mechanism behind pollution-induced reproductive failures in birds.

A test system was developed to examine the effects of environmental contaminants on thiamine homeostasis in bird embryos. This system employs fresh chicken egg yolk lipids as a vehicle for use in egg injection studies. Furazolidone, an antibiotic suspected to interfere with thiamine metabolism, was used as a positive control to evaluate the utility of the test system. It was determined that fresh chicken egg yolk lipids were preferable over chemical vehicles as it resulted in lower mortality rates (16% versus 23-62%) and did not induce any observable effects in the embryo. Injection of 1 mg/egg of furazolidone at day 0 of development resulted in decreased respiration followed by death, with mortality rates being twice as high as in carrier controls. In addition, transketolase activity, which was measured as an indicator of thiamine availability in the body, was decreased 25% in brains of 19-day-old embryos. This mechanism may be of importance for effects of environmental contaminants in wild bird populations.

Gas chromatographic determination of pemoline as 5-phenyl-2,4-oxazolidinedione in human urine.

A simple gas chromatographic assay of the psychostimulant pemoline in human urine has been developed. Instead of extraction of the drug from urine, it is hydrolysed to 5-phenyl-2,4-oxazolidinedione with 1 N hydrochloric acid. After the extraction, this compound is methylated with diazomethane and determined by gas-liquid chromatography using a nitrogen-selective detector and a solid injection system. The method has been applied in preliminary human pharmacokinetic studies, by measuring the urinary excretion rate of pemoline following oral administration. At present, the screening procedures for doping control do not involve the detection of pemoline, but the method described can easily be incorporated in such procedures.