Pharmacological activity of new imidazole-4,5-dicarboxylic acid derivatives in dopaminergic transmission suppression ttests in mice and rats

To study the antiparkinsonian activity of new 1,2-substituted imidazole-4,5-dicarboxylic acids in dopaminergic transmission suppression tests in mice and rat

Compliance assessment of ambulatory Alzheimer patients to aid therapeutic decisions by healthcare professionals

<p>Abstract</p> <p>Background</p> <p>Compliance represents a major determinant for the effectiveness of pharmacotherapy. Compliance reports summarising electronically compiled compliance data qualify healthcare needs and can be utilised as part of a compliance enhancing intervention. Nevertheless, evidence-based information on a sufficient level of compliance is scarce complicating the interpretation of compliance reports. The purpose of our pilot study was to determine the compliance of ambulatory Alzheimer patients to antidementia drugs under routine therapeutic use using electronic monitoring. In addition, the forgiveness of donepezil (i.e. its ability to sustain adequate pharmacological response despite suboptimal compliance) was characterised and evidence-based guidance for the interpretation of compliance reports was intended to be developed.</p> <p>Methods</p> <p>We determined the compliance of four different antidementia drugs by electronic monitoring in 31 patients over six months. All patients were recruited from the gerontopsychiatric clinic of a university hospital as part of a pilot study. The so called medication event monitoring system (MEMS) was employed, consisting of a vial with a microprocessor in the lid which records the time (date, hour, minute) of every opening. Daily compliance served as primary outcome measure, defined as percentage of days with correctly administered doses of medication. In addition, pharmacokinetics and pharmacodynamics of donepezil were simulated to systematically assess therapeutic undersupply also incorporating study compliance patterns. Statistical analyses were performed with SPSS and Microsoft Excel.</p> <p>Results</p> <p>Median daily compliance was 94% (range 48%-99%). Ten patients (32%) were non-compliant at least for one month. One-sixth of patients taking donepezil displayed periods of therapeutic undersupply. For 10 mg and 5 mg donepezil once-daily dosing, the estimated forgiveness of donepezil was 80% and 90% daily compliance or two and one dosage omissions at steady state, respectively. Based on the simulation findings we developed rules for the evidence-based interpretation of donepezil compliance reports.</p> <p>Conclusions</p> <p>Compliance in ambulatory Alzheimer patients was for the first time assessed under routine conditions using electronic monitoring: On average compliance was relatively high but variable between patients. The approach of pharmacokinetic/pharmacodynamic <it>in silico </it>simulations was suitable to characterise the forgiveness of donepezil suggesting evidence-based recommendations for the interpretation of compliance reports.</p

Application of pharmacokinetic-pharmacodynamic modeling in management of QT abnormalities after citalopram overdose. Reply to A. Manini

Sir, Manini et al. express concerns about the algorithm that we developed for the management of cardiotoxicity in citalopram overdose. We respond to their comments as follows:In the algorithm we use “dose estimate” and not “ingested dose”. The difference between the dose amount reported (based on the patient history, tablet counts and other available information) and the dose amount estimated in the modelling ranged from 0 to 75 mg, i.e. the reported dose amount was acceptably reliable [1].Of the three published cases that the authors quote where patients ingested less than 600 mg [2, 3, 4], two did not have an abnormal QT based on the QT nomogram derived from Fossa et al. [5, 6]. Bazett\u27s correction was used in these two cases despite its known overcorrection in patients with fast heart rates. In the third case, a patient was reported to have sinus tachycardia, but absolute QT and RR was not reported, in addition to an uncertainty in the reported dose [2]

Characterization of fullerene derivatives by MALDI fragment mass spectra

Зарегистрированы и обсуждены масс-спектры фуллерена CMALDI and MALDI LIFT-TOF/TOF mass spectra of fullerene