Constantin Mircioiu

Physiologically motivated time-delay model to account for mechanisms underlying enterohepatic circulation of piroxicam in human beings.

The study was conducted to formulate a physiologically motivated time-delay (PM TD) mathematical model for human beings, which incorporates disintegration of a drug formulation, dissolution, discontinuous gastric emptying and enterohepatic circulation (EHC) of a drug. Piroxicam, administered to 24 European, healthy individuals in 20 mg capsules Feldene Pfizer, was used as a model drug. Plasma was analysed for piroxicam by a validated high-performance liquid chromatography method. The PM TD mathematical model was developed using measured plasma piroxicam concentration-time profiles of the individuals and tools of a computationally efficient mathematical analysis and modeling, based on the theory of linear dynamic systems. The constructed model was capable of (i) quantifying different fractions of the piroxicam dose sequentially disposable for absorption and (ii) estimating time delays between time when the piroxicam dose reaches stomach and time when individual of fractions of the piroxicam dose is disposable for absorption. The model verification was performed through a formal proof, based on comparisons of observed and model-predicted plasma piroxicam concentration-time profiles. The model verification showed an adequate model performance and agreement between the compared profiles. Accordingly, it confirmed that the developed model was an appropriate representative of the piroxicam fate in the individuals enrolled. The presented model provides valuable information on factors that control dynamic mechanisms of EHC, that is, information unobtainable with the models proposed for the EHC analysis previously.

Evaluation of in vitro absorption, decontamination and desorption of organophosphorous compounds from skin and synthetic membranes.

Chemical warfare agents, such as soman, and pesticides, such as chlorpyrifos, dichlorvos or malathion, are toxic organophosphorous compounds (OPCs) that are readily absorbed by the skin. Decontamination using solvents or surfactants may modify the cornified layer - the skins main barrier against xenobiotic penetration. Thus, effective skin decontamination with fewer side effects is desired. We determined the membrane absorption, decontamination and desorption of toxic OPCs using human skin and synthetic membrane (cuprophane, cellulose acetate, methyl ethyl cellulose, acetophane and nylon) models, and estimated the efficacy of adsorptive powders (bentonite and magnesium trisilicate) at inhibiting this transfer. Using validated flow-through and static diffusion cell and HPLC methods, we found that the transfer of OPCs depends on their membrane affinity. The chlorpyrifos transfer decreased with a decrease in the membrane hydrophilicity, and that of malathion across hydrophilic membranes was less than half of that across hydrophobic membranes. We reliably modeled the toxicant transfer through the skin and synthetic membranes as first-order kinetic and/or square root law transfer processes, suggesting a potential application of synthetic membranes for predicting percutaneous absorption of OPCs. All tested adsorptive powders, applied either alone or as mixtures, significantly reduced the toxicant amount transferred across all membrane models, suggesting a potential therapeutic application with fewer later undesired effects on intact skin.

The PHAR-QA Project: Competency Framework for Pharmacy Practice—First Steps, the Results of the European Network Delphi Round 1

PHAR-QA, funded by the European Commission, is producing a framework of competences for pharmacy practice. The framework is in line with the EU directive on sectoral professions and takes into account the diversity of the pharmacy profession and the on-going changes in healthcare systems (with an increasingly important role for pharmacists), and in the pharmaceutical industry. PHAR-QA is asking academia, students and practicing pharmacists to rank competences required for practice. The results show that competences in the areas of “drug interactions”, “need for drug treatment” and “provision of information and service” were ranked highest whereas those in the areas of “ability to design and conduct research” and “development and production of medicines” were ranked lower. For the latter two categories, industrial pharmacists ranked them higher than did the other five groups.

What is a Pharmacist: Opinions of Pharmacy Department Academics and Community Pharmacists on Competences Required for Pharmacy Practice

This paper looks at the opinions of 241 European academics (who provide pharmacy education), and of 258 European community pharmacists (who apply it), on competences for pharmacy practice. A proposal for competences was generated by a panel of experts using Delphi methodology. Once finalized, the proposal was then submitted to a large, European-wide community of academics and practicing pharmacists in an additional Delphi round. Academics and community pharmacy practitioners recognized the importance of the notion of patient care competences, underlining the nature of the pharmacist as a specialist of medicines. The survey revealed certain discrepancies. Academics placed substantial emphasis on research, pharmaceutical technology, regulatory aspects of quality, etc., but these were ranked much lower by community pharmacists who concentrated more on patient care competences. In a sub-analysis of the data, we evaluated how perceptions may have changed since the 1980s and the introduction of the notions of competence and pharmaceutical care. This was done by splitting both groups into respondents < 40 and > 40 years old. Results for the subgroups were essentially statistically the same but with some different qualitative tendencies. The results are discussed in the light of the different conceptions of the professional identity of the pharmacist.

The Second Round of the PHAR-QA Survey of Competences for Pharmacy Practice

This paper presents the results of the second European Delphi round on the ranking of competences for pharmacy practice and compares these data to those of the first round already published. A comparison of the numbers of respondents, distribution by age group, country of residence, etc., shows that whilst the student population of respondents changed from Round 1 to 2, the populations of the professional groups (community, hospital and industrial pharmacists, pharmacists in other occupations and academics) were more stable. Results are given for the consensus of ranking and the scores of ranking of 50 competences for pharmacy practice. This two-stage, large-scale Delphi process harmonized and validated the Quality Assurance in European Pharmacy Education and Training (PHAR-QA) framework and ensured the adoption by the pharmacy profession of a framework proposed by the academic pharmacy community. The process of evaluation and validation of ranking of competences by the pharmacy profession is now complete, and the PHAR-QA consortium will now put forward a definitive PHAR-QA framework of competences for pharmacy practice.

A Comparison of Parametric and Non-Parametric Methods Applied to a Likert Scale

A trenchant and passionate dispute over the use of parametric versus non-parametric methods for the analysis of Likert scale ordinal data has raged for the past eight decades. The answer is not a simple “yes” or “no” but is related to hypotheses, objectives, risks, and paradigms. In this paper, we took a pragmatic approach. We applied both types of methods to the analysis of actual Likert data on responses from different professional subgroups of European pharmacists regarding competencies for practice. Results obtained show that with “large” (>15) numbers of responses and similar (but clearly not normal) distributions from different subgroups, parametric and non-parametric analyses give in almost all cases the same significant or non-significant results for inter-subgroup comparisons. Parametric methods were more discriminant in the cases of non-similar conclusions. Considering that the largest differences in opinions occurred in the upper part of the 4-point Likert scale (ranks 3 “very important” and 4 “essential”), a “score analysis” based on this part of the data was undertaken. This transformation of the ordinal Likert data into binary scores produced a graphical representation that was visually easier to understand as differences were accentuated. In conclusion, in this case of Likert ordinal data with high response rates, restraining the analysis to non-parametric methods leads to a loss of information. The addition of parametric methods, graphical analysis, analysis of subsets, and transformation of data leads to more in-depth analyses.

Novel approach to bioequivalence assessment based on physiologically motivated model

The study was conducted to exemplify an approach capable of obtaining a new insight into bioequivalence (BE) assessment, by the use of a physiologically motivated model. Data from an oral BE study of two piroxicam (PXM) products was used as an example. The BE study was carried out with 24 healthy European subjects according to a two-sequence crossover-randomized design. The test and reference formulations were a PXM generic formulation (LaborMed Pharma, Romania) and Feldene (Pfizer, USA), respectively. Plasma concentrations of PXM were monitored by a validated high-performance liquid chromatography over a period of 144 h after administration. After the structure of the optimal model was selected, parameters that characterized the whole-body disposition behavior of PXM in the subjects were derived. The paired Students t-test and Wilkoxons test were performed on the derived parameters. The null hypothesis of no differences in the parameters of the whole-body disposition behavior of PXM related to the test and reference product was not rejected at 5% level of significance. This result suggested that the compared products were bioequivalent and could be used interchangeably in clinical setting. The presented approach might show a new way, worth incorporating in future BE guidelines.

Does the subject content of the pharmacy degree course influence the community pharmacist’s views on competencies for practice?

Do community pharmacists coming from different educational backgrounds rank the importance of competences for practice differently—or is the way in which they see their profession more influenced by practice than university education? A survey was carried out on 68 competences for pharmacy practice in seven countries with different pharmacy education systems in terms of the relative importance of the subject areas chemical and medicinal sciences. Community pharmacists were asked to rank the competences in terms of relative importance for practice; competences were divided into personal and patient-care competences. The ranking was very similar in the seven countries suggesting that evaluation of competences for practice is based more on professional experience than on prior university education. There were some differences for instance in research-related competences and these may be influenced, by education.

How Do European Pharmacy Students Rank Competences for Practice

European students (n = 370), academics (n = 241) and community pharmacists (n = 258) ranked 13 clusters of 68 personal and patient care competences for pharmacy practice. The results show that ranking profiles for all three groups as a rule were similar. This was especially true of the comparison between students and community pharmacists concerning patient care competences suggesting that students have a good idea of their future profession. A comparison of first and fifth (final) year students shows more awareness of patient care competences in the final year students. Differences do exist, however, between students and community pharmacists. Students—like academics—ranked competences concerned with industrial pharmacy and the quality aspects of preparing drugs, as well as scientific fundamentals of pharmacy practice, well above the rankings of community pharmacists. There were no substantial differences amongst rankings of students from different countries although some countries have more “medicinal” courses than others. This is to our knowledge the first paper to look at how, within a healthcare sectoral profession such as pharmacy, the views on the relative importance of different competences for practice of those educating the future professionals and their students, are compared to the views of working professionals.

Hospital and Community Pharmacists’ Perceptions of Which Competences Are Important for Their Practice

The objective of the PHAR-QA (Quality assurance in European pharmacy education and training) project was to investigate how competence-based learning could be applied to a healthcare, sectoral profession such as pharmacy. This is the first study on evaluation of competences from the pharmacists’ perspective using an improved Delphi method with a large number of respondents from all over Europe. This paper looks at the way in which hospital pharmacists rank the fundamental competences for pharmacy practice. European hospital pharmacists (n = 152) ranked 68 competences for pharmacy practice of two types (personal and patient care), arranged into 13 clusters. Results were compared to those obtained from community pharmacists (n = 258). Generally, hospital and community pharmacists rank competences in a similar way. Nevertheless, differences can be detected. The higher focus of hospital pharmacists on knowledge of the different areas of science as well as on laboratory tests reflects the idea of a hospital pharmacy specialisation. The difference is also visible in the field of drug production. This is a necessary competence in hospitals with requests for drugs for rare diseases, as well as paediatric and oncologic drugs. Hospital pharmacists give entrepreneurship a lower score, but cost-effectiveness a higher one than community pharmacists. This reflects the reality of pharmacy practice where community pharmacists have to act as entrepreneurs, and hospital pharmacists are managers staying within drug budgets. The results are discussed in the light of a “hospital pharmacy” specialisation.