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2.
Am J Pharm Educ ; 86(5): 8567, 2022 06.
Article in English | MEDLINE | ID: mdl-34521617

ABSTRACT

Objective. To expand our understanding of student engagement by qualitatively examining how student pharmacists experienced the psychological state of engagement when applying team-based learning (TBL) pedagogy.Methods. A qualitative case study was conducted. Data were obtained through semi-structured interviews with a purposeful and convenience sample of student pharmacists (n=14). Our initial data analysis identified common themes for student engagement in TBL. We then characterized each common theme by deductively coding the themes into predetermined focal concepts of engagement based upon Kearsley and Shneiderman's 1 previous characterization of student engagement as either relate, create, or donate components.Results. Seven common themes arose from this research: accountability, communication, conflict, learning, preparation, purpose, and teamwork. Results indicated that student pharmacists engaged in TBL pedagogy mostly experience the psychological state of student engagement through a relate (41%) component by drawing on team support and trust, followed by the donate (32%) and create (27%) components.Conclusion. Findings in this study are consistent with other research on TBL pedagogy which concluded that, at least in part, this type of learning was a conduit for building student pharmacists' engagement skills. The novelty of this research is that it deductively characterized how student pharmacists perceive, comprehend, and interpret the psychological state of engagement in TBL. Specifically, our findings concluded student pharmacists mostly identify with a relate component of engagement by drawing on team support and trust developed from TBL tenets that encourage communication, conflict resolution, and teamwork.


Subject(s)
Education, Pharmacy , Curriculum , Education, Pharmacy/methods , Humans , Pharmacists , Problem-Based Learning/methods , Students
3.
Health Serv Insights ; 14: 11786329211058283, 2021.
Article in English | MEDLINE | ID: mdl-34880625

ABSTRACT

The opioid epidemic continues to be an ongoing public health crisis. Many primary health care providers aptly serve as the gatekeeper to opioid prescriptions. The opioid epidemic has challenged the primary care profession whilst many of these providers have opted out of opioid prescribing altogether. This unintended consequence affirms erosion to primary care that is vital to the ecosystem of opioid management. The purpose of this study was to understand strategies to deliver opioids safely and effectively. Results indicate primary care providers are uniquely positioned to make a positive opioid impact through focused change initiatives. Five common themes arose from the inductive analysis: (1) provide leadership support; (2) define standard of work; (3) conduct pre-visit reviews; (4) conduct post-visit reviews; and (5) measure progress. Then, each common theme was deductively analyzed through a view of Kotter's change theory to support an effective proxy for implementing and sustaining chronic opioid therapy in a primary care context. These finding have potential to provide actionable implications for health care management professionals and primary care organizations such as hospitals and group practices.

4.
Curr Pharm Teach Learn ; 13(2): 116-121, 2021 02.
Article in English | MEDLINE | ID: mdl-33454066

ABSTRACT

INTRODUCTION: Critical thinking is an important ability for pharmacists, but few studies have found improvements in pharmacy student critical thinking skills as a consequence of their education. Team-based learning (TBL) is an active learning strategy that encourages students to think critically to solve problems. The purpose of this study was to evaluate the impact of TBL on the critical thinking skills of pharmacy students. METHODS: One hundred ninety students from the first two cohorts at a pharmacy school were invited to participate. The Health Science Reasoning Test (HSRT) was administered prior to the first semester and after two years of the TBL-based pharmacy curriculum. Student's t-test was used for a pairwise analysis along with Welch's t-test for unequal variances when comparing HSRT score modulation. RESULTS: There was an overall increase in mean HSRT score. However, some participants (29%) with initially higher mean HSRT scores did not demonstrate an increase. Nearly all (99%) participants demonstrated improvements of one of the eight domains of critical thinking evaluated in the HSRT. This corresponded with an improvement in score of the majority of participants (n = 115). CONCLUSION: This study provides evidence that TBL improves critical thinking skills. More research is needed to identify the specific aspects of TBL that influence critical thinking.


Subject(s)
Education, Pharmacy , Students, Pharmacy , Educational Measurement , Humans , Learning , Schools, Pharmacy , Thinking
5.
Am J Pharm Educ ; 83(3): 7456, 2019 04.
Article in English | MEDLINE | ID: mdl-31065173

ABSTRACT

Objective. To characterize how virtual reality (VR) has been and is being used in pharmacy education, and evaluate the projected utility of VR technology in pharmacy education in the future. Findings. Virtual reality technology has been used in pharmacy education for many years to provide engaging learning experiences. Although these learning experiences were not available in the three-dimensional digital environments provided by current VR, they demonstrated improvements in learning. Recent technological advancements have substantially increased the potential usefulness of VR for pharmacy education by providing immersive educational activities that mimic real world experiences to reinforce didactic and laboratory concepts. Virtual reality training that uses head-mounted displays is just beginning in pharmacy education, but more educational VR programs are becoming available. Further research will be necessary to fully understand the potential impact of VR on pharmacy education. Summary. Virtual reality technology can provide an immersive and interactive learning environment, overcoming many of the early challenges faced by instructors who used virtual activities for pharmacy education. With further technological and software development, VR has the potential to become an integral part of pharmacy education.


Subject(s)
Education, Pharmacy/methods , Education, Pharmacy/trends , Virtual Reality , Humans , Models, Educational , Problem-Based Learning , Simulation Training/methods , Software
6.
J Pharm Pharm Sci ; 22(1): 22-27, 2019.
Article in English | MEDLINE | ID: mdl-30599819

ABSTRACT

The American Diabetic Association standards of medical care for diabetic patients recommends moderate intensity exercise to help manage diabetes; however, this recommendation may be unmanageable for patients who have become inactive or unable to reach this intensity. The purpose of this review is to determine if low-intensity exercises demonstrate improvement in diabetic peripheral neuropathy symptoms in order to utilize these exercises as a starting point for inactive patients. Studies in low-intensity exercises from 2013 to May 2018 were systematically searched in PubMed, SCOPUS, and Cochrane Library databases. The studies in this research have shown that low-intensity resistance exercises have promising outcomes such as improvements in pain interference with daily activities, pain thresholds, and reductions in neuropathy symptoms. Low-intensity aerobic therapy adds to the quality of life of the patient, and increases in strength of the lower limbs show an improvement in foot sensation and a reduction in pain and tingling symptoms.


Subject(s)
Diabetic Neuropathies/rehabilitation , Exercise Therapy , Diabetic Neuropathies/physiopathology , Exercise , Humans , Postural Balance
7.
Curr Pharm Teach Learn ; 10(10): 1384-1390, 2018 10.
Article in English | MEDLINE | ID: mdl-30527368

ABSTRACT

BACKGROUND AND PURPOSE: Online distance education has become popular in pharmacy education, but it can be challenging to provide engaging experiences such as team-based learning (TBL) in this format. This study explored the utility of virtual reality (VR) as a platform to provide the engaging elements of TBL, without students needing to be physically present in the same room. EDUCATIONAL ACTIVITY AND SETTING: Volunteers participated in a modified TBL exercise in VR, followed by a survey of the experience. The survey included Likert-type questions to evaluate the level of immersion and perceived engagement, comfort and desirability of VR-TBL experiences. FINDINGS AND DISCUSSION: The majority of the responses to the 14-question survey were 'agree' or 'strongly agree'. Ninety-four percent (94.4%) of participants strongly agreed that this was a fun experience, and 94.4% of participants strongly agreed that they would take a course in this format if it was offered. Although none of the questions received a majority of 'disagree' or 'strongly disagree' responses, areas for improvement included ease of use of the technology, comfort and improving the learning activity. SUMMARY: The response of participants to this study was positive and the overall conclusion was that VR has the potential to be a useful tool for online, distance TBL, and should be explored further.


Subject(s)
Education, Distance/standards , Problem-Based Learning/standards , Virtual Reality , Adult , Curriculum/standards , Education, Distance/methods , Education, Distance/trends , Education, Pharmacy/methods , Education, Pharmacy/standards , Education, Pharmacy/statistics & numerical data , Educational Measurement/methods , Educational Measurement/statistics & numerical data , Female , Humans , Male , Problem-Based Learning/methods , Problem-Based Learning/trends , Surveys and Questionnaires , Texas
8.
J Pharm Pharm Sci ; 21(1s): 177s-191s, 2018.
Article in English | MEDLINE | ID: mdl-30139425

ABSTRACT

PURPOSE: The aim of this systematic review is to evaluate current evidence of alpha-lipoic acid (ALA) regarding efficacy, safety, and cost to accurately compare it with other diabetic polyneuropathy (DPN) treatments. The intention is to provide recommendations on future research and to promote utilization of ALA in the United States (US). METHODS: A literature search was conducted on three databases: Scopus, PubMed, and Web of Science. The following criteria were used to select studies: (1) randomized controlled trials (RCTs) and open-label trials on ALA, (2) review articles and meta-analyses of RCTs on ALA, (3) study population consisting of patients with diabetes mellitus, peripheral neuropathic pain, and/or metabolic syndrome. RESULTS: Twenty-five publications were selected including five RCTs and three open-label studies. Most clinical trials were conducted outside of the US. Current data provides evidence for the benefits of ALA in DPN treatment at a dose of 600 mg per day, either intravenously (IV) or orally, for a duration of at least 3 weeks with minimal side effects. CONCLUSIONS: ALA demonstrates effectiveness in treating DPN through multiple mechanisms to modulate pathophysiology and control symptoms. In addition, ALA exhibits activity in weight management and insulin sensitivity. The use of ALA for DPN in the US is worth considering because commonly prescribed medications have unclear mechanisms, more pronounced adverse effects, and are more expensive than ALA.  Further research needs to be conducted to assess long-term efficacy of ALA in US patients.


Subject(s)
Diabetic Neuropathies/drug therapy , Thioctic Acid/therapeutic use , Humans , Molecular Conformation , Thioctic Acid/administration & dosage , Thioctic Acid/chemistry
9.
AIDS ; 32(5): 613-622, 2018 03 13.
Article in English | MEDLINE | ID: mdl-29280758

ABSTRACT

OBJECTIVE: To compare prevalence of insulin resistance between perinatally HIV-infected (PHIV+) and perinatally HIV-exposed, but uninfected adolescents (PHEU), determine incidence of and contributory factors to new and resolved cases of insulin resistance in PHIV+, and evaluate glucose metabolism. DESIGN: Cross-sectional design for comparison of prevalence among PHIV+ and PHEU. Longitudinal design for incidence and resolution of insulin resistance among PHIV+ at risk for these outcomes. METHODS: The source population was adolescents from pediatric HIV clinics in the United States and Puerto Rico participating in the Pediatric HIV/AIDS Cohort Study, an ongoing prospective cohort study designed to evaluate impact of HIV infection and its treatment on multiple domains in preadolescents and adolescents. Insulin resistance was assessed by homeostatic model assessment of insulin resistance. Those with incident insulin resistance underwent 2-h oral glucose tolerance test and HbA1c. Baseline demographic, metabolic, and HIV-specific variables were evaluated for association with incident or resolved insulin resistance. RESULTS: Unadjusted prevalence of insulin resistance in PHIV+ was 27.3 versus 34.1% in PHEU. After adjustment for Tanner stage, age, sex, and race/ethnicity, there was no significant difference between groups. Factors positively associated with developing insulin resistance included female sex, higher BMI z score, and higher waist circumference; those associated with resolving insulin resistance included male sex and lower BMI z score. CONCLUSION: Prevalence of insulin resistance in PHIV+ and PHEU was substantially higher than that reported in HIV-uninfected nonoverweight youth, but similar to that in HIV-uninfected obese youth. Factors associated with incident or resolved insulin resistance among PHIV+ were similar to those reported in HIV-negative obese youth. However, a contributory role of HIV infection and/or its treatment to the incident risk of insulin resistance cannot be excluded.


Subject(s)
HIV Infections/complications , Insulin Resistance , Adolescent , Child , Cross-Sectional Studies , Female , Glucose Tolerance Test , Glycated Hemoglobin/analysis , Humans , Incidence , Longitudinal Studies , Male , Prevalence , Prospective Studies , Puerto Rico , Time Factors , United States
10.
AIDS ; 31(1): 15-23, 2017 01 02.
Article in English | MEDLINE | ID: mdl-27755108

ABSTRACT

OBJECTIVE: To identify relationships between insulin resistance (IR) and mitochondrial respiration in perinatally HIV-infected youth. DESIGN: Case-control study. METHODS: Mitochondrial respiration was assessed in perinatally HIV-infected youth in Tanner stages 2-5, 25 youth with IR (IR+) and 50 without IR (IR-) who were enrolled in the Pediatric HIV/AIDS Cohort Study. IR was defined as a homeostatic model of assessment for IR value at least 4.0. A novel, high-throughput oximetry method was used to evaluate cellular respiration in peripheral blood mononuclear cells. Unadjusted and adjusted differences in mitochondrial respiration markers between IR+ and IR- were evaluated, as were correlations between mitochondrial respiration markers and biochemical measurements. RESULTS: IR+ and IR- youth were similar on age, sex, and race/ethnicity. Mean age was 16.5 and 15.6 years in IR+ and IR-, respectively. The IR+ group had significantly higher mean BMI and metabolic analytes (fasting glucose, insulin, cholesterol, triglycerides, and venous lactate and pyruvate) compared with the IR-. Mitochondrial respiration markers were, on average, lower in the IR+ compared with IR-, including basal respiration (417.5 vs. 597.5 pmol, P = 0.074), ATP production (11 513 vs. 15 202 pmol, P = 0.078), proton leak (584.6 vs. 790.0 pmol, P = 0.033), maximal respiration (1815 vs. 2399 pmol, P = 0.025), and spare respiration capacity (1162 vs. 2017 pmol, P = 0.032). Nonmitochondrial respiration did not differ by IR status. The results did not change when adjusted for age. CONCLUSION: HIV-infected youth with IR have lower mitochondrial respiration markers when compared to youth without IR. Disordered mitochondrial respiration may be a potential mechanism for IR in this population.


Subject(s)
Cell Respiration , HIV Infections/complications , Insulin Resistance , Leukocytes, Mononuclear/metabolism , Mitochondria/metabolism , Adolescent , Case-Control Studies , Child , Female , Humans , Male
11.
J Pharm Pharm Sci ; 18(4): 713-27, 2015.
Article in English | MEDLINE | ID: mdl-26626255

ABSTRACT

PURPOSE: Delineate the selected pharmacodynamics of a naturally occurring stilbene 3'-Hydroxypterostilbene. OBJECTIVE: Characterize for the first time the pharmacodynamics bioactivity in several in-vitro assays with relevant roles in heart disease, inflammation, cancer, and diabetes etiology and pathophysiology. METHODS: 3'-Hydroxypterostilbene was studied in in-vitro assays to identify possible bioactivity. RESULTS: 3'-Hydroxypterostilbene demonstrated anti-oxidant, anti-inflammatory, cytotoxic, anti-adipogenic, histone deacetylase, and sirtuin-1 inhibitory activity. CONCLUSIONS: The importance of understanding individual stilbene pharmacologic activities were delineated. Small changes in chemical structure of stilbene compounds result in significant pharmacodynamic differences. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Stilbenes/pharmacology , 3T3-L1 Cells , Adipogenesis/drug effects , Animals , Cell Line, Tumor , Histone Deacetylases/metabolism , Humans , Mice , Neoplasms/drug therapy , Neoplasms/pathology , Sirtuin 1/antagonists & inhibitors
12.
Phytother Res ; 29(8): 1168-79, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25939395

ABSTRACT

Studies were undertaken to evaluate the bioavailability in rats and content analysis of gnetol in Gnetum gnemon products reported to contain gnetol and to examine the pharmacological properties of gnetol in in vitro models including anti-inflammatory/analgesic, antidiabetic, anti-adipogenesis, and anticancer activity. Male Sprague-Dawley rats were cannulated and dosed either intravenously with gnetol (10 mg/kg) or orally (100 mg/kg). Various methanolic extractions of G. gnemon products were quantified. Gnetol's effect on cell viability in selected cell lines with or without inflammatory stimulus was assessed. α-Amylase and α-glucosidase inhibition was evaluated. Cyclooxygenase (COX)-1, COX-2, and histone deacetylase inhibition and adipogenesis inhibition were examined. After oral and intravenous administration, gnetol was detected in both serum and urine as the parent compound and as a glucuronidated metabolite. The bioavailability of gnetol was determined to be 6%. Gnetol is rapidly glucuronidated and is excreted in urine and via nonrenal routes. Gnetol was found to exist as an aglycone and as a glycoside in G. gnemon products. Gnetol showed concentration-dependent reductions in cell viability in cancer cell lines with greatest activity in colorectal cancer and potent COX-1, histone deacetylase, and weak COX-2 activities along with limited reduction in inflammation. Gnetol also possessed concentration-dependent alpha-amylase, alpha-glucosidase, and adipogenesis activities. Pretreatment of mice with gnetol was able to increase the latency period to response in analgesia models.


Subject(s)
Enzyme Inhibitors/pharmacokinetics , Food Analysis , Gnetum/chemistry , Stilbenes/pharmacokinetics , Animals , Antioxidants/pharmacology , Biological Availability , Cell Line, Tumor , Cyclooxygenase 1 , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors/pharmacokinetics , Glycoside Hydrolase Inhibitors/pharmacology , Humans , Male , Membrane Proteins/antagonists & inhibitors , Mice , Pain/drug therapy , Rats , Rats, Sprague-Dawley , Stilbenes/blood , Stilbenes/urine , alpha-Amylases/antagonists & inhibitors , alpha-Glucosidases
13.
Biomed Chromatogr ; 27(3): 404-6, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22815238

ABSTRACT

Pharmacometric characterization studies of liquiritigenin have historically overlooked its chiral nature. To achieve complete characterization, an analytical method enabling the detection and quantification of the individual enantiomers of racemic (±) liquiritigenin is necessary. Resolution of the enantiomers of liquiritigenin was achieved using a simple high-performance liquid chromatographic method. A Chiralpak® ADRH column was employed to perform baseline separation with UV detection at 210 nm.The standard curves were linear ranging from 0.5 to 100 µg/mL for each enantiomer. Limit of quantification was 0.5 µg/mL. The assay was applied successfully to stereoselective serum disposition of liquiritigenin enantiomers in rats. Liquiritigenin enantiomers were detected in serum as both aglycones and glucuronidated conjugates. Both unconjugated enantiomers had a serum half-life of ~15 min in rats. The volume of distribution (V(d) ) for S- and R-liquiritigenin was 1.49 and 2.21 L/kg, respectively. Total clearance (Cl(total) ) was 5.12 L/h/kg for S-liquiritigenin and 4.79 L/h/kg for R-liquiritigenin, and area under the curve (AUC(0-inf) ) was 3.95 µg h/mL for S-liquiritigenin and 4.23 µg h/mL for R-liquiritigenin. The large volume of distribution coupled with the short serum half-life suggests extensive distribution of liquiritigenin into tissues.


Subject(s)
Chromatography, High Pressure Liquid/methods , Flavanones/blood , Animals , Area Under Curve , Chromatography, Reverse-Phase/methods , Flavanones/chemistry , Flavanones/pharmacokinetics , Linear Models , Male , Rats , Rats, Sprague-Dawley , Sensitivity and Specificity , Stereoisomerism
14.
Biomed Chromatogr ; 27(5): 548-50, 2013 May.
Article in English | MEDLINE | ID: mdl-23070926

ABSTRACT

The complete pharmacokinetic disposition of the chiral flavonoid (±) pinostrobin remains unknown without the development of an analytical method of detection and quantitation of its individual enantiomers. Resolution of the enantiomers of pinostrobin was achieved using as simple high-performance liquid chromatographic method. A Chiralpak(®) AD-RH column was employed to perform baseline separation with UV detection at 287 nm. The standard curves were linear ranging from 0.5 to 100 µg/mL for each enantiomer. The limit of quantification was 0.5 µg/mL. Precision and accuracy of the assay was < 15% (RSD) and was with a bias <15% for all points on the calibration curve. The assay was applied successfully to stereoselective serum disposition of pinostrobin enantiomers in rats. Both enantiomers had a serum half-life of ~7 h. They also shared similar values of volume of distribution (V(d) S-pinostrobin, 8.2 L/kg; V(d) R-pinostrobin, 8.9 L/kg), total clearance (S-pinostrobin CL(total), 0.959 L//h/kg; R-pinostrobin CL(total), 1.055 L//h/kg), and area under the curve (S-pinostrobin AUC(inf), 23.16 µg h/mL; R-pinostrobin AUC(inf), 21.296 µg h/mL). The large volume of distribution suggests extensive distribution of pinostrobin into tissues.


Subject(s)
Flavanones/blood , Flavanones/pharmacokinetics , Animals , Chromatography, High Pressure Liquid , Flavanones/chemistry , Least-Squares Analysis , Male , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Sensitivity and Specificity , Stereoisomerism
15.
Biomed Chromatogr ; 27(6): 681-4, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23212747

ABSTRACT

An analytical method enabling the detection and quantification of the individual enantiomers of racemic (±) pinocembrin is required to fully characterize its pharmacokinetic disposition. Direct resolution of the enantiomers of pinocembrin was achieved using a novel and simple reversed-phase high-performance liquid chromatography method with electrospray ionization and detection by mass spectrometry in rat serum. A Chiralcel® AD-RH column was employed to perform baseline separation with electrospray positive-mode ionization with selected ion monitoring detection. The standard curves were linear from 0.5 to 100 µg/mL for each enantiomer. The limit of quantification was 0.5 µg/mL. The assay was applied successfully to stereoselective serum disposition of pinocembrin enantiomers in rats. Pinocembrin enantiomers were detected in serum. Both enantiomers had a serum half-life of ~15 min in rats. Similar values of volume of distribution between the enantiomers were also observed: 1.76 L/kg for S-pinocembrin and 1.79 L/kg for R-pinocembrin. Total clearance was 5.527 L//h/kg for S-pinocembrin and 5.535 L/h/kg for R-pinocembrin, and the area under the curve was 1.821 µg h/mL for S-pinocembrin and 1.876 µg h/mL for R-pinocembrin. The large volume of distribution coupled with the short serum half-life suggests extensive distribution of pinocembrin into the tissues.


Subject(s)
Flavanones/pharmacokinetics , Animals , Chromatography, High Pressure Liquid/methods , Chromatography, Reverse-Phase/methods , Coumarins/chemistry , Flavanones/blood , Flavanones/chemistry , Least-Squares Analysis , Male , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Sensitivity and Specificity , Spectrometry, Mass, Electrospray Ionization/methods , Stereoisomerism
16.
J Pharm Sci ; 101(10): 3787-98, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22806441

ABSTRACT

The histone deacetylase inhibitor suberoylanilide hydroxamic acid, known as vorinostat, is a promising anticancer drug with a unique mode of action; however, it is plagued by low water solubility, low permeability, and suboptimal pharmacokinetics. In this study, poly(ethylene glycol)-b-poly(DL-lactic acid) (PEG-b-PLA) micelles of vorinostat were developed. Vorinostat's pharmacokinetics in rats was investigated after intravenous (i.v.) (10 mg/kg) and oral (p.o.) (50 mg/kg) micellar administrations and compared with a conventional polyethylene glycol 400 solution and methylcellulose suspension. The micelles increased the aqueous solubility of vorinostat from 0.2 to 8.15 ± 0.60 and 10.24 ± 0.92 mg/mL at drug to nanocarrier ratios of 1:10 and 1:15, respectively. Micelles had nanoscopic mean diameters of 75.67 ± 7.57 and 87.33 ± 8.62 nm for 1:10 and 1:15 micelles, respectively, with drug loading capacities of 9.93 ± 0.21% and 6.91 ± 1.19%, and encapsulation efficiencies of 42.74 ± 1.67% and 73.29 ± 4.78%, respectively. The micelles provided sustained exposure and improved pharmacokinetics characterized by a significant increase in serum half-life, area under curve, and mean residence time. The micelles reduced vorinostat clearance particularly after i.v. dosing. Thus, PEG-b-PLA micelles significantly improved the p.o. and i.v. pharmacokinetics and bioavailability of vorinostat, which warrants further investigation.


Subject(s)
Hydroxamic Acids/chemistry , Hydroxamic Acids/pharmacokinetics , Lactates/chemistry , Nanoparticles/chemistry , Polyethylene Glycols/chemistry , Animals , Biological Availability , Delayed-Action Preparations , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Half-Life , Hydroxamic Acids/blood , Hydroxamic Acids/urine , Lactates/administration & dosage , Male , Methylcellulose/administration & dosage , Methylcellulose/chemistry , Micelles , Nanoparticles/administration & dosage , Particle Size , Polyethylene Glycols/administration & dosage , Rats , Rats, Sprague-Dawley , Solubility , Suspensions/administration & dosage , Suspensions/chemistry , Suspensions/pharmacokinetics , Vorinostat
17.
Biomed Chromatogr ; 26(5): 606-9, 2012 May.
Article in English | MEDLINE | ID: mdl-21898475

ABSTRACT

A method for analysis of lacosamide [(R)-2-acetamido-N-benzyl-3-methoxypropionamide] is needed for both human and veterinary pharmacokinetic investigations. While lacosamide is currently used to manage partial-onset seizures in humans suffering from epilepsy, it is also presently being investigated for use in the treatment of canine epilepsy in veterinary medicine. Currently, no dosing regimen for the drug exists in dogs. A novel and simple high-performance liquid chromatography method was developed for determination of lacosamide in dog serum. Serum proteins (0.1 mL) were precipitated with -20.0°C acetonitrile after addition of the internal standard, daidzein. Separation was achieved with a Phenomenex® Luna® C18 (2) (5 µm, 250 × 4.60 mm) column with ultraviolet detection at 210 nm. The calibration curves were linear ranging from 0.5 to 25 µg/mL. Precision of the assay was <13% (RSD) and was within 12% for all points in the calibration curve. The limit of quantitation for this method was 0.5 µg/mL. The assay was applied successfully to a pre-clinical study of lacosamide pharmacokinetics in dogs.


Subject(s)
Acetamides/blood , Anticonvulsants/blood , Chromatography, High Pressure Liquid/methods , Dogs/blood , Spectrophotometry, Ultraviolet/methods , Acetamides/pharmacokinetics , Animals , Anticonvulsants/pharmacokinetics , Chromatography, Reverse-Phase , Drug Stability , Lacosamide , Linear Models
18.
Pharmaceutics ; 5(1): 81-93, 2012 Dec 27.
Article in English | MEDLINE | ID: mdl-24300398

ABSTRACT

The rapamycin analog, ridaforolimus, has demonstrated potent anti-proliferative effects in cancer treatment, and it currently is being evaluated in a range of clinical cancer studies. Ridaforolimus is an extremely lipophilic compound with limited aqueous solubility, which may benefit from formulation with polymeric micelles. Herein, we report the encapsulation of ridaforolimus in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000) (DSPE-PEG2000) via a solvent extraction technique. Micelle loading greatly improved the solubility of ridaforolimus by approximately 40 times from 200 µg/mL to 8.9 mg/mL. The diameters of the drug-loaded micelles were 33 ± 15 nm indicating they are of appropriate size to accumulate within the tumor site via the enhanced permeability and retention (EPR) effect. The DSPE-PEG2000 micelle formulation was dosed intravenously to rats at 10 mg/kg and compared to a control of ridaforolimus in ethanol/PEG 400. The micelle significantly increased the half-life of ridaforolimus by 170% and decreased the clearance by 58%, which is consistent with improved retention of the drug in the plasma by the micelle formulation.

19.
J Pharm Sci ; 100(6): 2064-70, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21491436

ABSTRACT

The purpose of this investigation was to study the pharmacokinetics and nephrotoxicity of amphotericin B (AmB), incorporated in poly(ethylene glycol)-block-poly(N-hexyl stearate l-aspartamide) (PEG-b-PHSA) micelles (AmB/PEG-b-PHSA). After AmB/PEG-b-PHSA or AmB for injection, United States Pharmacopeia (USP), was dosed intravenously in rats (0.8 mg/kg), serum was collected over 72 h, and organs collected at 72 h for AmB analysis. To test for the nephrotoxicity caused by AmB, renal markers of damage were assessed 24 h after a single injection of AmB/PEG-b-PHSA or AmB for injection, USP, focusing on detection of urinary enzymes. PEG-b-PHSA micelles caused a significantly lower area under serum concentration curve and higher clearance relative to AmB for injection, USP. PEG-b-PHSA micelles lowered the distribution of AmB in liver and lung tissues, but did not significantly lower the level of AmB in the kidneys relative to AmB for injection, USP. However, urine levels of N-acetyl-ß-glucosaminidase and γ-glutamyltransferase were significantly lower for AmB/PEG-b-PHSA relative to AmB for injection, USP. In summary, PEG-b-PHSA micelles reduced the nephrotoxicity of AmB, the dose-limiting toxicity of this important antifungal agent.


Subject(s)
Amphotericin B , Antifungal Agents , Drug Carriers/chemistry , Kidney/drug effects , Polyesters/chemistry , Polyethylene Glycols/chemistry , Amphotericin B/administration & dosage , Amphotericin B/adverse effects , Amphotericin B/pharmacokinetics , Animals , Antifungal Agents/administration & dosage , Antifungal Agents/adverse effects , Antifungal Agents/pharmacokinetics , Drug Compounding , Kidney Function Tests , Male , Micelles , Organ Specificity , Rats , Rats, Sprague-Dawley , Tissue Distribution
20.
Chirality ; 23(4): 339-48, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21384439

ABSTRACT

The chirality of flavonoids has been overlooked in the majority of pharmacokinetic studies of homoeriodictyol, isosakuranetin, and taxifolin. The stereospecific pharmacokinetic disposition of these xenobiotics in male Sprague-Dawley rats is described for the first time. Validated HPLC methods were used to analyze serum and urine samples of rats following intravenous administration of each flavonoid via jugular vein cannulation and to determine their content in selected fruits. The characterization and interpretation of the pharmacokinetic disposition profiles of homoeriodictyol, isosakuranetin, and taxifolin are described. A discrepancy exists between half-lives in serum and urine which may be attributed to low assay sensitivity in serum for the three compounds; thus, a more accurate estimation of the pharmacokinetic parameters was obtained from urine. The pharmacokinetics of homoeriodictyol, isosakuranetin, and taxifolin revealed distribution, metabolism, and elimination that were dependent on the stereochemistry of the stereoisomers. The (-)-(S)-enantiomers of homoeriodictyol and isosakuranetin and the (+)-(2S; 3R)-stereoisomer of taxifolin were predominant in lemon, grapefruit, and tomato. These findings were achieved using chiral methods of analysis; the utility and necessity of developing chiral methods of analysis for chiral xenobiotics are discussed.


Subject(s)
Flavones/analysis , Flavones/pharmacokinetics , Flavonoids/analysis , Flavonoids/pharmacokinetics , Fruit/chemistry , Quercetin/analogs & derivatives , Animals , Area Under Curve , Chromatography, High Pressure Liquid/methods , Drug Stability , Half-Life , Male , Molecular Structure , Quercetin/analysis , Quercetin/pharmacokinetics , Rats , Rats, Sprague-Dawley , Serum/chemistry , Stereoisomerism , Urine/chemistry
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