Peter C. Panus

Transdermal iontophoretic delivery of ketoprofen through human cadaver skin and in humans

Abstract Transdermal iontophoretic delivery of ketoprofen in cadaver skin and healthy volunteers was examined. In vitro anodic and cathodic iontophoresis (0.5 mA/cm 2 , 3 h) of ketoprofen (75 mg/ml) resulted in equivalent intracutaneous ketoprofen permeation (232.1 ± 27.1 vs. 275.0 ± 141.0 μ g/cm 2 , respectively), which in turn was higher than passive intracutaneous uptake of ketoprofen (40.7 ± 42.1 μ g/cm 2 ). In contrast, only cathodic iontophoresis resulted in transcutaneous ketoprofen permeation across cadaver skin, under these conditions. The in vitro study was then repeated to achieve transcutaneous permeation of ketoprofen at clinical iontophoretic parameters (0.28 mA/cm 2 , 40 min) by increasing drug concentration to 300 mg/ml. No stereo-selective permeation of R - and S -ketoprofen enantiomers was observed in vitro. In humans, cathodic iontophoresis of 300 mg/ml ketoprofen (0.28 mA/cm 2 , 40 min) was performed at the wrist. Ketoprofen was detected at 40 min (0.88 ± 0.42 μ g/ml) from the forearm veins of the ipsilateral arm. Urinary excretion of ketoprofen totaled 790 ± 170 μ g at 16 h post iontophoresis. This investigation is the first to clearly demonstrate transcutaneous iontophoresis of an antiinflammatory agent in humans utilizing a commercially cleared iontophoretic device. The investigation also adds to the very limited number of publications in the area of iontophoretic delivery of drugs to humans.

Pharmacy Student Self-Testing as a Predictor of Examination Performance

Objectives. To determine if student self-testing improves performance during a doctor of pharmacy course. Methods. Students were given access to online quizzes with a large pool of randomly selected questions specific to upcoming examination content. Quizzes were electronically scored immediately upon completion and students were provided corrective feedback. Results. Examination scores following implementation of the practice quizzes were significantly higher in all but the last testing period. The upper fiftieth percentile of students scored higher on both the practice quizzes and subsequent examinations in all but the fourth testing period. Conclusions. Providing pharmacy students with self-testing opportunities could increase their retention of course material and provide feedback to both students and educators regarding learning, as well as provide students with a measure of their metacognition.

Student Performance in a Pharmacotherapy Oncology Module Before and After Flipping the Classroom

Objective. To determine if a flipped classroom improved student examination performance in a pharmacotherapy oncology module. Design. Third-year pharmacy students in 2012 experienced the oncology module as interactive lectures with optional case studies as supplemental homework. In 2013, students experienced the same content in a primarily flipped classroom. Students were instructed to watch vodcasts (video podcasts) before in-class case studies but were not held accountable (ie, quizzed) for preclass preparation. Examination questions were identical in both cohorts. Performance on examination questions was compared between the two cohorts using analysis of covariance (ANCOVA), with prior academic performance variables (grade point average [GPA]) as covariates. Assessment. The students who experienced the flipped classroom approach performed poorer on examination questions than the cohort who experienced interactive lecture, with previous GPA used as a covariate. Conclusion. A flipped classroom does not necessarily improve student performance. Further research is needed to determine optimal classroom flipping techniques.

Tissue extraction and high-performance liquid chromatographic determination of ketoprofen enantiomers

Local transcutaneous delivery of non-steroidal anti-inflammatory drugs avoids gastrointestinal side effects and concentrates drugs in the intended tissues. An extraction and HPLC method was developed for ketoprofen in skin, fascia and muscle. Tissue samples were homogenized in NaHCO3. After methylene chloride removal of lipids, the aqueous layer was acidified with HCl and back extracted into isooctane/isopropanol. Ketoprofen was derivatized with ethylchloroformate/S-(-)-alpha-phenylethylamine in triethylamine, then detected by HPLC. Ketoprofen recovery was linear (1-33 microg/g) and was detected in these tissues following in vivo cathodic iontophoresis (160 mA*min). This represents the first non-radioactive method for determination of ketoprofen in tissues following transcutaneous iontophoresis.

Effects of rebamipide on nephrotoxicity associated with selected NSAIDs in rats

Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is primarily limited by renal and gastrointestinal adverse effects. Rebamipide suppresses gastric mucosal injury when administered with NSAIDs. This study aimed to determine rebamipides influence upon renal effects following concomitant use with celecoxib or diclofenac. On day 0, rats were randomly divided into 6 groups (n≥6). On days 1 and 2, three groups received placebo and three groups were administered rebamipide (30 mg/kg) twice daily. On day 3, the rats treated with placebo received another dose of placebo and ten minutes later a single dose of celecoxib (40 mg/kg), diclofenac (10mg/kg), or placebo, respectively. The rats treated with rebamipide received one more dose of rebamipide and ten minutes later one single dose of celecoxib, diclofenac, or placebo, respectively. Urine and blood samples were collected on days 0, 2, and 3. Sodium and potassium excretion rates decreased significantly in the rats treated with celecoxib, diclofenac, rebamipide plus celecoxib, or rebamipide plus diclofenac on day 3. Blood urea nitrogen (BUN) levels significantly increased in placebo plus diclofenac and rebamipide plus diclofenac groups on day 3. Comparing the two groups, the levels of BUN was significantly higher in the rebamipide plus diclofenac group compared to that of placebo plus diclofenac group. Concomitant administration of rebamipide with either NSAID caused a rise in concentrations of urinary kidney injury molecule-1. Histopathological evaluations revealed an intensified NSAID-induced tubular necrosis by rebamipide. Based upon the results obtained, concomitant administration of rebamipide with NSAIDs enhances the effect of NSAIDs on tubular injury.

A Subgroup Analysis of the Impact of Self-testing Frequency on Examination Scores in a Pathophysiology Course

Objective: To determine if the frequency of self-testing of course material prior to actual examination improves examination scores, regardless of the actual scores on the self-testing. Methods: Practice quizzes were randomly generated from a total of 1342 multiple-choice questions in pathophysiology and made available online for student self-testing. Intercorrelations, 2-way repeated measures ANOVA with post hoc tests, and 2-group comparisons following rank ordering, were conducted. Results: During each of 4 testing blocks, more than 85% of students took advantage of the self-testing process for a total of 7042 attempts. A consistent significant correlation (p≤0.05) existed between the number of practice quiz attempts and the subsequent examination scores. No difference in the number of quiz attempts was demonstrated compared to the first testing block. Exam scores for the first and second testing blocks were both higher than those for third and fourth blocks. Conclusion: Although self-testing strategies increase retrieval and retention, they are uncommon in pharmacy education. The results suggested that the number of self-testing attempts alone improved subsequent examination scores, regardless of the score for self-tests.

Exacerbation of Celecoxib-Induced Renal Injury by Concomitant Administration of Misoprostol in Rats

Nonsteroidal anti-inflammatory drugs (NSAIDs) can produce adverse effects by inhibiting prostaglandin (PG) synthesis. A PGE1 analogue, misoprostol, is often utilized to alleviate NSAID-related gastrointestinal side effects. This study examined the effect of misoprostol on celecoxib renal toxicity. Additionally, the effects of these drugs on cardiovascular parameters were evaluated. Four randomized rat groups were orally gavaged for 9 days, two groups receiving vehicle and two groups receiving misoprostol (100 µg/kg) twice daily. Celecoxib (40 mg/kg) was co-administered once daily to one vehicle and one misoprostol group from days 3 to 9. Urine and blood samples were collected and blood pressure parameters were measured during the study period. Hearts and kidneys were harvested on final day. Day 2 urinary electrolyte samples revealed significant reductions in sodium excretion in misoprostol (0.12±0.05 µmol/min/100 g) and misoprostol+celecoxib groups (0.07±0.02 µmol/min/100 g). At day 3, all treatment groups showed significantly reduced sodium excretion. Potassium excretion diminished significantly in vehicle+celecoxib and misoprostol+celecoxib groups from day 3 onward. Urinary kidney injury molecule-1 levels were significantly increased in vehicle+celecoxib (0.65±0.02 vs. 0.35±0.07 ng/mL, p = 0.0002) and misoprostol+celecoxib (0.61±0.06 vs. 0.37±0.06 ng/mL, p = 0.0015) groups when compared to baseline; while plasma levels of cardiac troponin I increased significantly in vehicle+celecoxib (p = 0.0040) and misoprostol+misoprostol (p = 0.0078) groups when compared to vehicle+vehicle. Blood pressure parameters increased significantly in all misoprostol treated groups. Significant elevation in diastolic (p = 0.0071) and mean blood pressure (p = 0.0153) was noted in misoprostol+celecoxib compared to vehicle+celecoxib. All treatments produced significant tubular dilatation/necrosis compared to control. No significant myocardial changes were noticed; however, three animals presented with pericarditis. Kidney, heart, and plasma celecoxib levels revealed no significant change between vehicle+celecoxib and misoprostol+celecoxib. Concomitant misoprostol administration did not prevent celecoxib renal toxicity, and instead exacerbated renal side effects. Misoprostol did not alter plasma or tissue celecoxib concentrations suggesting no pharmacokinetic interaction between celecoxib and misoprostol.

Development and evaluation of the Medication-based Index of physical Function (MedIP)

Background the development of an objective and comprehensive drug-based index of physical function for older adults has the potential to more accurately predict fall risk. Design the index was developed using 862 adults (ages 57-85) from the National Social Life, Health, and Aging Project (NSHAP) Wave 1 study. The index was evaluated in 70 adults (ages 51-88) from a rehabilitation study of dizziness and balance. Methods the prevalence among 601 drugs for 1,694 side effects was used with fall history to determine the magnitude of each side effects contribution towards physical function. This information was used to calculate a Medication-based Index of Physical function (MedIP) score for each individual based on his or her medication profile. The MedIP was compared to the timed up and go (TUG) test as well as drug counts using receiver operating characteristic (ROC) analysis. The associations between various indices of physical function and MedIP were calculated. Results within the NSHAP data set, the MedIP was better than drug counts or TUG at predicting falls based on ROC analysis. Using scores above and below the cutpoint, the MedIP was a significant predictor of falls (OR = 2.61 [95% CI 1.83, 3.64]; P < 0.001). Using an external data set, it was shown that the MedIP was significantly correlated with fall number (P = 0.044), composite physical function (P = 0.026) and preferred gait speed (P = 0.043). Conclusion the MedIP has the potential to become a useful tool in the healthcare and fall prevention of older individuals.

Visual biofeedback training reduces quantitative drugs index scores associated with fall risk

ObjectiveDrugs increase fall risk and decrease performance on balance and mobility tests. Conversely, whether biofeedback training to reduce fall risk also decreases scores on a published drug-based fall risk index has not been documented. Forty-eight community-dwelling older adults underwent either treadmill gait training plus visual feedback (+VFB), or walked on a treadmill without feedback. The Quantitative Drug Index (QDI) was derived from each participant’s drug list and is based upon all cause drug-associated fall risk. Analysis of covariance assessed changes in the QDI during the study, and data is presented as mean ± standard error of the mean.ResultsThe QDI scores decreased significantly (p = 0.031) for participants receiving treadmill gait training +VFB (− 0.259 ± 0.207), compared to participants who walked on the treadmill without VFB (0.463 ± 0.246). Changes in participants QDI scores were dependent in part upon their age, which was a significant covariate (p = 0.007). These preliminary results demonstrate that rehabilitation to reduce fall risk may also decrease use of drugs associated with falls. Determination of which drugs or drug classes that contribute to the reduction in QDI scores for participants receiving treadmill gait training +VFB, compared to treadmill walking only, will require a larger participant investigation.Trial Registration ISRNCT01690611, ClinicalTrials.gov #366151-1, initial 9/24/2012, completed 4/21/2016

Self-Testing Improves Exam Scores Regardless of Self-Testing Average

Objective: The utilization of interprofessional education and collaborative practice delivers optimal health services and improves patient outcomes. Training future healthcare providers in an integrated environment promotes a “collaborative practice-ready” workforce. The aim of this study was to identify ongoing specific interprofessional collaborative projects and promote their awareness among faculty at the St. John Fisher College Wegmans School of Pharmacy. Methods: Faculty members were surveyed to identify the ongoing interprofessional collaborative initiatives among pharmacy faculty. Results: A total of four collaborative practices were identified among faculty: ambulatory care, assistedliving, didactic, and assessment. The ambulatory care setting at an osteoporosis clinic provides patientcentered care with a clinical component. Each patient with a new diagnosis or change in medication therapy receives education/counseling from a pharmacist, a registered nurse for medication administration and a physician for a physical exam. In the assisted-living setting, pharmacy and nursing students are paired to conduct a high-level health assessment in their respective disciplines. Didactic interprofessional efforts are being conducted to create a flexible and comprehensive pain education curriculum. Physicians, dentists, nurses, pharmacists, psychologists, chiropractors, and oriental medicine practitioners will develop the curriculum. The pain module will be adaptable for interprofessional education activities. Finally, recognizing the similarities in accreditation standards for communication and professionalism, the School of Pharmacy and the NY Chiropractic School are sharing strategies and rubrics for assessing these outcomes. Implications: The survey revealed a broader range of interprofessional collaborations than was originally suspected. The school will continue to foster and support interprofessional education and collaborative practice. Disciplines Pharmacy and Pharmaceutical Sciences Comments Poster presented at: • Annual meeting of the American Association of Colleges of Pharmacy in Orlando, Florida, July, 2012. • Faculty Scholarship Celebration at St. John Fisher College in Rochester, New York, October 25, 2012. Abstract is published in American Journal of Pharmaceutical Education 2012; 76 (5) Article 99. https://doi.org/10.5688/ajpe76599is published in American Journal of Pharmaceutical Education 2012; 76 (5) Article 99. https://doi.org/10.5688/ajpe76599 Authors David Hutchinson, Jane M. Souza, Jennifer Mathews, Anthony Corigliano, Katherine Juba, Jill Lavigne, Andrea Traina, Karen A. Bobak, Constance Baldwin, and O.J. Sahler This poster presentation is available at Fisher Digital Publications: https://fisherpub.sjfc.edu/pharmacy_facpub/20 THE CROSSROADS OF INTERPROFESSIONALISM: Four Avenues of Collaboration at the Wegmans School of Pharmacy at St. John Fisher College David Hutchinson, Pharm.D.; Jane Souza, Ph.D.; Jennifer Mathews, Ph.D.; Anthony Corigliano, R.Ph.; Katherine Juba, Pharm.D.; Jill Lavigne, Ph.D.; Andrea Traina, Pharm.D.; Karen A. Bobak D.C. Constance Baldwin, Ph.D.; O.J. Sahler, M.D.