Effective Interventions for Diabetes Patients by Community Pharmacists: A Meta-analysis of Pharmaceutical Care Components.

OBJECTIVE: To evaluate randomized controlled trials (RCTs) that included interventions provided by community pharmacists for patients with type 1 and 2 diabetes, the analysis of each component of the intervention(s), and the description of the training that the pharmacists received. DATA SOURCES: The literature research was conducted in PubMed and in the Cochrane Central Register of Controlled Trials (January 2000 to April 2016) for RCTs with interventions provided by community pharmacists for patients with diabetes. Corresponding authors were contacted about missing data and intervention and training design. STUDY SELECTION AND DATA EXTRACTION: RCTs published in English or German were included if pharmaceutical care or medication therapy management was conducted by community pharmacists with diabetes patients. Basic information, intervention and training design data were extracted. DATA SYNTHESIS: The literature research resulted in 11 eligible studies for further analysis. The corresponding authors of 6 studies responded to our request and sent their raw data. The calculated meta-analytical effect of 640 analyzed patients was a hemoglobin A1C (A1C) difference of -0.66%, with a 95% CI of -0.86% to -0.45%. The analysis revealed that most intervention elements had a significant positive meta-analytical effect on the A1C values. CONCLUSIONS: Our meta-analysis suggests that community pharmacist-led interventions can improve glycemic control in patients with type 1 and 2 diabetes. The most effective intervention components were patient centered and interdisciplinary. Pharmaceutical care interventions should, therefore, include the following components: sending feedback to the physician, setting individual goals, reviewing medication, and assessing patients' health beliefs and medication knowledge.

Simultaneous quantitative and qualitative analysis of aliskiren, enalapril and its active metabolite enalaprilat in undiluted human urine utilizing LC-ESI-MS/MS.

The benefit-risk ratio of combined blocking by the direct renin inhibitor aliskiren and an angiotensin-converting enzyme inhibitor (e.g. enalapril) on the renin-angiotensin-aldosterone system is discussed. No method was available for simultaneous determination of both drugs in urine. A novel sensitive method for simultaneous quantification in undiluted human urine was developed which enables systematic pharmacokinetic investigations, especially in poorly investigated populations like children. Matrix effects were clearly reduced by applying solid-phase extraction followed by a chromatographic separation on Xselect(TM) C18 CSH columns. Mobile phase consisted of methanol and water, both acidified with formic acid. Under gradient conditions and a flow rate of 0.4 mL/min the column effluent was monitored by tandem mass spectrometry with electrospray ionization. Calibration curves were constructed in the range of 9.4-9600 ng/mL regarding aliskiren, 11.6-12000 ng/mL for enalapril and 8.8-9000 ng/mL for enalaprilat. All curves were analyzed utilizing 1/x(2) -weighted quadratic squared regression. Intra-run and inter-run precision were 3.2-5.8% and 6.1-10.3% for aliskiren, 2.4-6.1% and 3.9-7.9% for enalapril as well as 3.1-9.4% and 4.7-12.7% regarding enalaprilat. Selectivity, accuracy and stability results comply with current international bioanalysis guidelines. The fully validated method was successfully applied to a pharmacokinetic investigation in healthy volunteers.

Development of a Theoretical Continuous Glucose Monitoring Module for Pharmacy Students: Preparing Pharmacists for the Future.

To enhance the digital competencies of pharmacy students, the Institute of Clinical Pharmacy and Pharmacotherapy at Heinrich-Heine University Duesseldorf developed and evaluated a theoretical module on digital health and data analysis. This innovative module integrated a continuous glucose-monitoring (CGM) wearable device into teaching, providing students with in-depth practical experience and a 2.5 h seminar on digital health and CGM systems. Students' knowledge of CGM and self-assessment of their CGM competencies were assessed in a pre-post manner. Additionally, students' satisfaction with the module and their perceptions of the future integration of digital health training and the role of wearables in pharmacy practice were also assessed after the module. A total of 39 final-year pharmacy students completed the module conducted in June 2024 as part of the clinical pharmacy seminar. In total, 32 students completed the pre- and post-knowledge tests and self-assessment questionnaires. Both the knowledge and the students' self-assessment of CGM-related skills after the module increased significantly (p < 0.05). Students expanded their knowledge regarding digital health solutions, in particular the CGM systems, and increased their self-reported competence in CGM-related skills. With this module, an important foundation was laid, as this is the first theoretical module including the essentials of CGM digital health tools for pharmacy students in Germany.

Development and Evaluation of Interprofessional High-Fidelity Simulation Course on Medication Therapy Consultation for German Pharmacy and Medical Students-A Randomized Controlled Study.

Recently, there has been a remarkable move towards interprofessional collaboration in response to the COVID-19 pandemic and the care of comorbidities. In Germany, there has been a gradual increase in interprofessional learning in medical and pharmacy education, aiming to enhance patient care. To adapt the pharmacy curriculum for collaborative practice between pharmacy and medical students, we developed an immersive interprofessional collaboration course for pharmacy students using adult and pediatric high-fidelity simulators (HFS) to assess and train medication consultation skills. In a randomized controlled trial, we investigated whether interprofessional training between pharmacy and medical students results in differences in pharmacy students' performance of medication therapy consultation compared to the case of mono-professional training of pharmacy students only. Before and after inter/mono-professional training, each pharmacy student performed an objective structured clinical examination (OSCE) and completed a self-assessment questionnaire. Additionally, an attitude survey towards interprofessional learning was completed by pharmacy and medical students at the end of the training. As expected, interprofessional as well as mono-professional training showed a statistically significant increase in medication consultation skills. Of importance, the performance in the interprofessional training group was significantly better than in the mono-professional group, particularly in drug therapy counselling and consultation behaviors. There was a significant difference between the intervention and control groups in self-assessment scores, and all study participants had positive attitudes toward interprofessional collaboration and training. Therefore, interprofessional training using HFS has been shown to appropriately train pharmacy students for collaborative practice and consultation skills.

Vaccination Training for Pharmacy Undergraduates as a Compulsory Part of the Curriculum?-A Multicentric Observation.

In order to increase vaccination rates, the Government of Germany introduced vaccination against influenza and COVID-19 into the regular care administered by pharmacists. However, vaccination training is yet not integrated into the German pharmacy curriculum. Therefore, the Institute for Clinical Pharmacy and Pharmacotherapy in Duesseldorf had developed an innovative vaccination course using high-fidelity simulation for students. To investigate the acceptance further, the course was carried out at three different German universities (Bonn, Duesseldorf, Greifswald). Students were asked to give their self-assessment before and after and satisfaction only after the training course. Responses from 33 participants from the University of Bonn, 42 from the University of Duesseldorf and 49 from the University of Greifswald were analyzed. Every participant at the respective universities showed a significant increase in their self-assessment and indicated a high level of satisfaction with the course. The results also did not differ significantly between the respective universities. Consequently, the results lead to the hypothesis that the satisfaction of pharmacy students with this kind of training using high-fidelity simulation is very high and attractive, and can be recommended for other German universities. The integration of such vaccination training into the German pharmacy curriculum might be a future step.

Determination of aliskiren in human serum quantities by HPLC-tandem mass spectrometry appropriate for pediatric trials.

The orally active direct renin inhibitor aliskiren is approved for the treatment of essential hypertension in adults. Analytical methods utilized in clinical studies on efficacy and safety have not been fully described in the literature but need a large sample volume ranging from 200 to 700 µL, rendering them unsuitable particularly for pediatric applications. In the assay presented only 100 µL of serum is needed for mixed-mode solid-phase extraction. The chromatographic separation was performed on Xselect(TM) C18 CSH columns with mobile phase consisting of methanol-water-formic acid (75:25:0.005, v/v/v) and a flow rate of 0.4 mL/min. Running in positive electrospray ionization and multiple reaction monitoring the mass spectrometer was set to analyze precursor ion 552.2 m/z [M + H](+) to product ion 436.2 m/z during a total run time of 5 min. The method covers a linear calibration range of 0.146-1200 ng/mL. Intra-run and inter-run precisions were 0.4-7.2 and 0.6-12.9%. Mean recovery was at least 89%. Selectivity, accuracy and stability results comply with current European Medicines Agency and Food and Drug Administration guidelines. This successfully validated LC-MS/MS method with a wide linear calibration range requiring small serum amounts is suitable for pharmacokinetic investigations of aliskiren in pediatrics, adults and the elderly.

Impact of a Digital Tool on Pharmacy Students' Ability to Perform Medication Reviews: A Randomized Controlled Trial.

Digital Medication Review Tools (DMRTs) are increasingly important in pharmacy practice. To ensure that young pharmacists are sufficiently competent to perform medication reviews after graduation, the introduction of DMRTs teaching in academic education is necessary. The aim of our study was to demonstrate the effect of DMRTs use on pharmacy students' performance when conducting a medication review (MR) in a randomized controlled pre-post design. Forty-one pharmacy students were asked to complete a MR within 60 min, followed by a 10-min consultation with (intervention group) and without a DMRT (control group). The MR performance was subdivided into four categories: communication skills, subjective and objective patient data, assessment, and plan. Performance was assessed using objective structured clinical examinations (OSCEs) and analytical checklists. With the use of DMRTs, the overall performance was improved by 17.0% compared to the control group (p < 0.01). Improvement through DMRTs was seen in the subcategories "Assessment" and "Plan". Furthermore, pharmacy students liked using DMRTs and felt more confident overall. Our study results demonstrate that DMRTs improve the performance of MRs, hence DMRTs should become an integral part of pharmacy curriculum. Consequently, digitally enabled pharmacists using DMRTs will be better prepared for their professional careers in pharmacy practice.

Development and Assessment of Innovative High-Fidelity Simulation Vaccination Course Integrating Emergency Cases for Pharmacy Undergraduates-A Randomized Controlled Study.

Recently, pharmacists in Germany were allowed to administer influenza and COVID-19 vaccines for people aged 12 years and older in order to increase vaccination coverage rates. In order to adapt the pharmacy curriculum for clinical practice, an innovative, vaccination training course using a high-fidelity simulator (HFS) was developed, implementing clinical scenarios to manage adverse events. In a randomized controlled trial using a pre and post design with pharmacy undergraduates, the intervention group interacted with an HFS, while the control group was trained with low-fidelity injection pads. Before and after the respective training, each participant went through an objective structured clinical examination (OSCE) and completed a self-assessment questionnaire and knowledge quiz. Both training methods showed a significant increase in skills, but there was also a significant greater increase in the intervention group when compared to the control group, particularly with respect to the vaccination process. Furthermore, every individual in the intervention group improved from the pre- to post-training OSCEs. Therefore, HFS has been proven to be an appropriate tool to train pharmacy students for the purposes of vaccine administration and to prepare for future challenges. Particularly, recognizing and managing adverse reactions can be addressed in a very effective way.

An integrated physiology-based model for the interaction of RAA system biomarkers with drugs.

The renin angiotensin aldosterone system (RAAS) is a paramount target for the pharmacological treatment of cardiovascular diseases. As modeling and simulation techniques are becoming increasingly utilized in cardiovascular research, our aim was to develop a physiology-based model that describes the effect of different drugs at different doses on the RAAS and integrates physiology-based description drug pharmacokinetics (PK). First, a basic RAAS model was developed in which equations for drug effects were included and missing parameters estimated. Next, a physiology-based PK model for enalapril and enalaprilat was developed and coupled to the RAAS model. Simulation of the effects of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aliskiren administration on angiotensins I and II did not reveal significant overestimation or underestimation. For all drugs, the error numerics were acceptable. The model also encompassed the PK of intravenous and oral enalapril and its conversion to enalaprilat. In summary, we report a physiology-based model for the interaction of the RAAS biomarkers angiotensin I and II with enalapril, benazepril, aliskiren, and losartan that allows for an adequate description of the RAAS response after single administration of the drugs. Such a comprehensive description may lead to a better understanding of the effects of pharmacological interventions in the RAAS.

Functions of mHealth Diabetes Apps That Enable the Provision of Pharmaceutical Care: Criteria Development and Evaluation of Popular Apps.

Personal digital health apps for managing diabetes should include functions that enable the provision of pharmaceutical care services and allow within-app communication with pharmacists and other healthcare providers, thereby improving patient outcomes. The primary aim of this study was to assess the functions of diabetes apps that were relevant to providing pharmaceutical care services (i.e., medication management, adherence, non-pharmacological management, interoperability, and communication). Sixteen criteria related to pharmaceutical care were developed and then used to assess ten popular diabetes apps. The highest numbers of pharmaceutical care criteria were met by the apps Diabetes:M and mySugr (11 criteria); Contour™Diabetes, Dario Health, and OneTouch Reveal® (ten); and DiabetesConnect and ESYSTA (nine); followed by Glucose Buddy (eight), meala (seven), and lumind (three). The most prevalent functions were related to promoting adherence and non-pharmacological management, but most criteria relevant to medication management were lacking. Five apps allowed within-app communication between patients and healthcare professionals (HCPs); however, no app included communication with pharmacists. High-quality diabetes apps are powerful tools to support pharmaceutical care and remotely monitor diabetes patients. Improvements are needed as they often lack many medication management functions, including within-app communication with HCPs (especially pharmacists). To maximize diabetes app use and improve outcomes, app developers should consider including pharmacists alongside other healthcare providers when customizing app designs.

Enalapril and Enalaprilat Pharmacokinetics in Children with Heart Failure Due to Dilated Cardiomyopathy and Congestive Heart Failure after Administration of an Orodispersible Enalapril Minitablet (LENA-Studies).

Angiotensin-converting enzyme inhibitors (ACEI), such as enalapril, are a cornerstone of treatment for pediatric heart failure which is still used off-label. Using a novel age-appropriate formulation of enalapril orodispersible minitablets (ODMTs), phase II/III open-label, multicenter pharmacokinetic (PK) bridging studies were performed in pediatric patients with heart failure due to dilated cardiomyopathy (DCM) and congenital heart disease (CHD) in five participating European countries. Children were treated for 8 weeks with ODMTs according to an age-appropriate dosing schedule. The primary objective was to describe PK parameters (area under the curve (AUC), maximal concentration (Cmax), time to reach maximal concentration (t-max)) of enalapril and its active metabolite enalaprilat. Of 102 patients, 89 patients (n = 26, DCM; n = 63 CHD) were included in the primary PK endpoint analysis. Rate and extent of enalapril and its active metabolite enalaprilat were described and etiology and age could be identified as potential PK modifying factors. The dosing schedule appeared to be tolerated well and did not result in any significant drug-related serious adverse events. The PK analysis and the lack of severe safety events supports the applied age-appropriate dosing schedule for the enalapril ODMTs.

Clinical Pharmacokinetics of Enalapril and Enalaprilat in Pediatric Patients-A Systematic Review.

Purpose: Enalapril has an established safety and efficacy in adults and is used in hypertension, heart failure, and renal failure. In pediatric patients, enalapril is labeled for children with hypertension and used off label in children with heart failure. The systematic literature search aims to assess the current knowledge about enalapril and its active metabolite enalaprilat pharmacokinetics in children as a basis for dose delineation for pediatric patients with heart failure. Methods: A systematic literature review was performed in the PubMed database using relevant keywords. Dose normalization of relevant pharmacokinetic parameters of the identified studies was done for comparison between different diseases and pediatric age groups. Results: The literature search has resulted in three pediatric pharmacokinetic studies of enalapril out of which Wells et al. reported about children with hypertension and Nakamura et al., and Llyod et al. presented data for pediatric heart failure patients. The area under the curve values of enalaprilat in hypertensive pediatric patients increased with respect to the age groups and showed maturation of body functions with increasing age. Dose normalized comparison with the heart failure studies revealed that although the pediatric heart failure patients of > 20 days of age showed the area under the curve a similar to that of hypertensive patients, two pediatric patients of very early age (<20 days) were presented with 5-6-fold higher area under the curve values. Conclusion: Data related to the pharmacokinetics of enalapril and enalaprilat in hypertensive patients and few data for young heart failure children are available. Comparison of dose normalized exposition of the active metabolite enalaprilat indicated similarities between heart failure and hypertensive patients and a potentially high exposition of premature patients but substantially more pharmacokinetic studies are required to have reliable and robust enalapril as well as enalaprilat exposures especially in pediatric patients with heart failure as a basis for any dose delineation.

Training Pharmacy Students in Self-Medication Counseling Using an Objective Structured Clinical Examination-Based Approach.

INTRODUCTION: Pharmacists play an important role in ensuring the safe, effective, and rational use of drugs in self-medication. Given the potential risks of self-medication, adequate training on self-medication counseling should be provided to pharmacy students during their academic education. Objective structured clinical examinations (OSCEs) could be used to train pharmacy students in these skills. This study evaluated the efficacy of an OSCE-based approach for training pharmacy students in self-medication counseling and communication skills. METHODS: This randomized controlled study was conducted among pharmacy students using a pre-post design. The intervention group completed OSCE-based self-medication training, while the control group collected counseling-relevant information from summaries of product characteristics of over-the-counter drugs. The counseling and communication skills of both groups before and after training were assessed by completing OSCEs. The participants completed a self-assessment questionnaire on self-confidence and self-perceived proficiency before each OSCE encounter and a satisfaction survey at the end of the seminar. RESULTS: Students were generally satisfied with the seminar. While the OSCE-trained group demonstrated significantly greater increases in counseling skills and self-confidence and self-perceived proficiency than the control group, both groups had similar increases in communication skills. CONCLUSION: The present study suggests that applying OSCEs as a learning tool for self-medication counseling is beneficial for improving students' counseling skills as well as self-confidence and self-perceived proficiency. These results support the inclusion of OSCEs in pharmacy education and highlight its potential to bridge gaps between knowledge and practice.

The Development of an Educational Video on Blood Pressure Measurement for Pharmacy Students.

INTRODUCTION: High blood pressure is an important worldwide health issue. Pharmacists can perform multifaceted tasks in hypertension management such as measuring blood pressure. In a time where the use of educational videos in health professions education has increased, an educational video might be an option for teaching blood pressure measurement skills to pharmacy students. This project aimed to develop an educational video tailored to pharmacy students on oscillometric blood pressure measurement in a community pharmacy setting that can be used as a self-instruction video. METHODS: The video was created with support from the university's multimedia center. The video development was roughly divided into pre-production, production, and post-production. Students' satisfaction with and perception of the video was surveyed. RESULTS: An 11-minute 33-second self-instruction video in the German language on proper oscillometric blood pressure measurement tailored for pharmacy students was created. Along with descriptive slides, the video delineates the necessary steps of blood pressure measurement in a community pharmacy setting in a role-play, to support students in communication with the patient. Results of a survey on the satisfaction and perception of the video from thirty-seven pharmacy students were included in the analysis and revealed that the video was well accepted by pharmacy students. Moreover, approximately 95% responded that instructional videos should be included in future pharmacy education. CONCLUSION: We successfully developed an educational video on oscillometric blood pressure measurement for a community pharmacy setting. This work is a valuable form of support for faculty members, who intend to develop educational videos. This might be of interest especially during the coronavirus disease 2019 (COVID-19) pandemic, where distance learning has become highly relevant.

Blended Learning on Blood Pressure Measurement: Investigating Two In-Class Strategies in a Flipped Classroom-Like Setting to Teach Pharmacy Students Blood Pressure Measurement Skills.

For reliable blood pressure measurement, various potential sources of inaccuracies need to be considered to avoid incorrect decision-making. Pharmacy students should be sensitized and taught the skill accordingly. One strategy to teach students' blood pressure measurement skills might be through a blended learning approach in a flipped classroom-like setting. With a randomized two-arm study among pharmacy students in their eighth semester, the required extent of in-class session in the scope of a blended learning approach in a flipped classroom-like setting was evaluated. Participants' self-confidence and self-perceived proficiency were evaluated through a survey, and participants' blood pressure measurement performance was assessed by objective structured clinical examination (OSCE). Participants' satisfaction with, and perception of, the flipped classroom were also surveyed. The extended in-class activities did not result in a significantly higher increase of participants' OSCE score and self-assessment score when compared to the brief in-class session. Both in-class sessions yielded a significant increase in the OSCE scores as well as in the self-assessment scores. Moreover, the teaching approaches were predominantly well-received by the students. The use of both flipped classroom-like approaches improved pharmacy students' blood pressure measurement performance, though the brief in-class session was sufficient. Students' self-confidence/self-perceived proficiency in blood pressure measurement skills increased similarly in both settings.

Blended learning: Improving the diabetes mellitus counseling skills of German pharmacy students.

INTRODUCTION: Pharmacists have the responsibility to conduct medication therapy management and appropriately counsel patients and physicians on medicines. Blended learning and objective structured clinical examinations (OSCEs) may have the potential to address these skills. This study aimed to assess whether a blended learning program consisting of e-learning and OSCEs could enhance pharmacy students' abilities to conduct pharmaceutical consultations with type 2 diabetes mellitus patients. METHODS: The blended learning program consisted of e-learning, formative OSCEs, and summative OSCEs. The e-learning aimed to bring the students to the same level of diabetes knowledge. The students' baseline consultation skills were measured by a summative pre-training OSCE. After the formative OSCEs, a summative post-training OSCE quantified the change in performance. During the pre- and post-training OSCEs, analytical checklists were used to assess consultation skills and a global rating scale assessed communication skills. Surveys were used to measure students' self-assessment and satisfaction. RESULTS: The study demonstrated significant improvement in students' pharmaceutical knowledge of diabetes mellitus, consultation performances on diabetes mellitus, and self-assessment scores. Most students responded positively on the satisfaction survey. CONCLUSIONS: This study demonstrated that a blended learning approach with e-learning and OSCEs can improve students' diabetes consultations and communication skills. These results support the use of this instructional technique for teaching patient counseling. Further studies should consider a control group to assess whether the improvement of the consultation performance is a result of the training or solely a learning effect due to the repetition of summative OSCEs.

Self-Instruction Video Versus Face-to-Face Instruction of Pharmacy Students' Skills in Blood Pressure Measurement.

A modern approach to clinical skill education is the use of educational videos, yet there is a shortage of literature investigating the effect of self-instruction videos (SIVs) in pharmacy students. Therefore, our objective was to investigate whether an SIV is non-inferior compared to face-to-face instruction (FTFI) in acquiring blood pressure measurement skills. The participants in this randomized controlled study were pharmacy students. The control group was taught by FTFI, while the intervention group watched an SIV. Before and after the instruction, the participants' performance was assessed by an objective structured clinical examination (OSCE). The participants completed a self-assessment survey before each OSCE session. Moreover, the participants' perception and satisfaction were assessed using another survey. The OSCE score and self-assessment score increased significantly from pre- to post-instruction in both groups. The SIV was non-inferior compared to FTFI in terms of the OSCE score, considering a predefined non-inferiority margin of -10%. The participants' self-assessment yielded inconclusive results for non-inferiority. Both instructional approaches were well received. Considering our findings, SIVs might be a valuable option for teaching pharmacy students' blood pressure measurement skills. However, depending on the skill intended to be taught, a combination of an instructional video with instructor-led teaching may be necessary.

Efficacy of an Objective Structured Clinical Examination Training Approach for Training Pharmacy Students in Diabetes Mellitus Counseling: A Randomized Controlled Trial.

Pharmacists' tasks are multifaceted and include, for example, vital counseling and communication skills. Objective Structured Clinical Examinations (OSCEs) could be used to train pharmacy students in these skills. Our study sought to determine the efficacy of our OSCE training approach for training pharmacy students' counseling and communication skills on diabetes mellitus compared to a control group. This randomized controlled study was conducted with pharmacy students using a pre-post-design. The intervention group completed diabetes OSCE training, while the control group solved diabetes patient cases using subjective, objective, assessment, and plan notes. Before and after the respective training, both groups completed OSCEs evaluating counseling and communication skills. Before each OSCE encounter, the participants completed a self-assessment questionnaire and, upon completion of the seminar, filled out a satisfaction survey. The OSCE-trained group demonstrated a significantly greater increase in counseling and communication skills and self-confidence than the control group. Both groups were generally satisfied with the seminar. These results demonstrate that our OSCE training approach allows for the effective training of pharmacy students' diabetes counseling and communication skills and suggests the inclusion of such a skill-based approach more widely in pharmacy students' education.

Relative Bioavailability of Enalapril Administered as Orodispersible Minitablets in Healthy Adults.

The angiotensin-converting enzyme inhibitor enalapril is commonly used to treat chronic heart failure in children. Because some children are unable to swallow capsules or tablets, a new, age-appropriate, orodispersible minitablet (ODMT) containing 1 mg of enalapril was developed within the EU-funded LENA (Labeling of Enalapril from Neonates up to Adolescents) consortium. In order to support the clinical evaluation of this new formulation in children, a relative bioavailability study was performed in healthy adults, comparing the bioavailability of enalapril in the ODMT with that of a reference product (RP) Renitec, a registered standard enalapril tablet formulation. In this open-label, randomized 3-way crossover study, 24 healthy subjects received a 10-mg enalapril dose administered as (1) 2 × 5-mg tablets of the RP swallowed with water, (2) 10 × 1-mg ODMT swallowed with water, and (3) 10 × 1 mg ODMT dispersed on the tongue. When the relative bioavailability of the ODMT formulation swallowed with water was compared with that of the RP, the estimated 90%CIs for the ratio of area under the concentration-time curve (AUC0-∞ ) and or peak concentration (Cmax ) of enalapril were 92.34% to 106.49% and 91.28% to 115.72%, respectively, which are within the accepted bioequivalence limits of 80% to 125%. Following dispersion of the ODMT in the mouth, a slightly higher Cmax for enalapril was observed as compared with the RP with an upper 90%CI of 127.57%, slightly exceeding the bioequivalence limit. Taken together, it was demonstrated that the method of administration of the ODMT, swallowed or dispersed, did not significantly affect the bioavailability of enalapril.

A feasibility study prior to an international multicentre paediatric study to assess pharmacokinetic/pharmacodynamic sampling and sample preparation procedures, logistics and bioanalysis.

BACKGROUND: Variability in pre-analytical procedures such as blood sampling, sample preparation and transport can substantially influence bioanalytical results and subsequently impair reliability of data gathered during clinical trials. Especially in vulnerable populations, all efforts should be made to facilitate high-quality data extraction excluding unnecessary or repeated intervention. METHODS: The EU-funded LENA project (Labeling of Enalapril from Neonates up to Adolescents) included a feasibility study in its preparatory procedures prior to first-in-child studies. Derived from a regular study visit, it encompassed all procedures, from sampling of two study-specific drugs and four sensitive humoral parameters to bioanalysis, to evaluate the quality of obtained samples and applicability of logistical and bioanalytical procedures. Drug administration to healthy adults was circumvented by pre-spiking the blood collection tubes with a drug solution. Five clinical sites were evaluated. RESULTS: Clinical teams' preparedness and applicability of required sampling procedures was investigated in 18 volunteers, on-site. 97% of collected pharmacokinetic (PK) samples and 93% of samples for humoral parameters were obtained eligibly. Results met expectations, though one team had to be re-trained and performed a re-run. Planned procedures for sampling, sample preparation, transport and analysis were found to be suitable for being applied within paediatric trials. CONCLUSION: The concept of the presented feasibility study that simultaneously assesses PK/PD sampling, sample preparation, logistics and bioanalysis proved to be a promising tool for trial preparation. It revealed improperly installed processes and bottlenecks that required adjustments prior to start of recruitment. It facilitated high-quality conduct from the first moment of paediatric pivotal studies.