Brian Henriksen

Pharmacokinetic considerations in Roux-en-Y gastric bypass patients

PURPOSE Pharmacokinetic considerations in patients who have undergone Roux-en-Y gastric bypass (RYGB) are explored. SUMMARY The prevalence of obesity, especially morbid obesity, has dramatically increased in recent years. In response, the number of bariatric surgeries performed has risen sharply, as this surgery is the technique demonstrated as being the most effective for sustained treatment of morbid obesity. RYGB, the most popular technique in the United States, combines the principle of restriction (dramatically decreasing stomach size) with malabsorption (bypassing the entire duodenum). It stands to reason that a decrease in gastric and intestinal absorptive surface area may considerably affect oral bioavailability of some drugs. Drugs that require a more acidic environment for absorption, uncoating, or activation and drugs that rely on intestinal transporters located in the duodenum for proper absorption would be most affected. Practitioners looking for guidance in tailoring pharmacotherapy to the RYGB patient will find little help in the primary literature at this time. Until more pharmacokinetic studies are available, practitioners may apply and log P of individual the principles of pK(a) drugs in the attempt to predict the potential impact of the RYGB on a drugs absorption. Likewise, if a drug relies on certain transporters located with highest frequency in the duodenum, alternative therapies can be selected that do not rely on such transport mechanisms for absorption. CONCLUSION The pK(a), log P, and intestinal transport mechanisms should be considered when determining which drugs may have altered pharmacokinetics in patients who have undergone RYGB.

Physicochemical characterization techniques for solid lipid nanoparticles: principles and limitations

Abstract Solid lipid nanoparticles (SLNs) are gaining importance due to numerous advantages they offer as a drug delivery system. SLN incorporate poorly soluble drugs, proteins, biologicals, etc. SLN are prepared by techniques like high-pressure homogenization, sonication and employs a wide range of lipids and surfactants. Physicochemical characterization techniques include particle size analysis, zeta potential and determination of crystallinity/polymorphism. Furthermore, drug loading and drug entrapment efficiency are common parameters used to test the efficiency of SLN. Most importantly, the functionality assay of SLN is essential to predict the activity and performance in vivo. The review presented discusses the importance of SLN in drug delivery with emphasis on principles and limitations associated with their physicochemical characterization.

Evaluation of Triazole-Chelated Lanthanides as Chemically Stabile Bioimaging Agents

Europium (Eu), dysprosium (Dy), samarium (Sm), and terbium (Tb) complexes were prepared using the neutral tridentate chelator 2,6-bis(1-benzyl-1,2,3-triazol-4-yl)pyridine and one equivalent of each lanthanide salt. The physicochemical, aerodynamic, and in vitro cellular properties of each lanthanide metal complex were studied to determine their viability as cell surface fluorescent probes. Each compound was characterized by electrospray ionization mass spectroscopy (ESI-MS), ultraperformance liquid chromatography (UPLC), differential scanning calorimetry (DSC), and thermogravimetic analysis (TGA). Upon excitation at 320 nm each complex displayed characteristic lanthanide-based fluorescence emission in the visible wavelength range with stokes shifts greater than 200 nm. Each complex was found to be chemically stable when exposed to pH range of 1-11 for 72 h and resistant to photobleaching. To simulate pulmonary administration of these fluorophores, the aerodynamic properties of the Eu and Tb complexes were determined using a next generation impactor (NGI). This measurement confirmed that the complexes retain their fluorescence emission properties after nebulization. Cellular cytotoxicity was determined on A-549 lung cancer cell line using methylthiazol tetrazolium (MTT) cytotoxicity assay at 24, 48, and 72 h postexposure to the complexes. The complexes showed a dose and time-dependent effect on the percent viability of the cells.

Postoperative Opioid Requirements Following Roux-en-Y Gastric Bypass in Patients Receiving Continuous Bupivacaine Through a Pump System: A Retrospective Review

Background Patients who undergo Roux-en-Y gastric bypass (RYGB) surgery have self-reported considerable postoperative pain, often requiring opioid administration. Objective To determine whether continuous delivery of local anesthetic via an infusion pump system decreased postoperative opioid usage in post-RYGB patients. Methods The electronic health record was used to identify and review 289 patients who underwent RYGB at our institution from January 2009 to October 2011. The treatment group received a continuous infusion of 0.375% bupivacaine administered by intraperitoneal soaker catheter for 48 hours via an infusion pump; the control group did not receive a pump or local anesthetic. Both groups received general anesthesia, nausea prophylaxis, and pain medication. Pain management consisted of opioid-containing patient-controlled analgesia (PCA) for the first 24 hours. Patients transitioned to supplemental intravenous opioid boluses, plus an oral opioid, for the remainder of their stay. Opioid use was measured in terms of morphine equivalents. Secondary outcomes included visual analog scale (VAS) pain scores and length of hospitalization. Results Morphine equivalents over the postoperative time period studied were significantly lower in the bupivacaine group than the control group (133 vs 106 mg, respectively; P = .001). There was no significant difference in VAS scores between the 2 groups (P = .80). Finally, the length of hospitalization between the 2 groups did not differ (P = .77). Conclusions We have shown that continuous infusion of bupivacaine, administered via a pain pump system, may have decreased postoperative opioid utilization. There were no differences in VAS scores or length of hospitalization between groups.

Creation of medicinal chemistry learning communities through enhanced technology and interdisciplinary collaboration.

Objectives. To build an integrated medicinal chemistry learning community of campus and distance pharmacy students though the use of innovative technology and interdisciplinary teaching. Design. Mechanisms were implemented to bring distance students into campus-based medicinal chemistry classrooms in real time, stimulate interaction between instructors and various student cohorts, and promote group work during class. Also, pharmacy clinician colleagues were recruited to contribute to the teaching of the 3 medicinal chemistry courses. Assessment. Student perceptions on the value of technology to build community and advance learning were gleaned from course evaluations, in class feedback, and conversations with class officers and student groups. Responses on a survey of second-year students confirmed the benefits of interdisciplinary content integration on engagement and awareness of the connection between drug chemistry and pharmacy practice. A survey of clinician colleagues who contributed to teaching the 3 medicinal chemistry courses found their views were similar to those of students. Conclusions. The purposeful use of technology united learners, fostered communication, and advanced content comprehension in 3 medicinal chemistry courses taught to campus and distance students. Teaching collaboration with pharmacy clinicians enhanced learner interest in course content and provided insight into the integrated nature of the profession of pharmacy.

Allelic frequencies of 60 pharmacogene variants assessed within a Burmese population residing in northeast Indiana, USA

AIM The aim of this study was to investigate 60 SNPs pertaining to drug metabolism and pharmacodynamics in the Burmese refugee population in the Fort Wayne, Indiana area to better inform patient care. MATERIALS & METHODS Sixty-two self-identified Burmese refugees were genotyped for 60 common SNPs pertaining to pharmacokinetic and pharmacodynamic pharmacogenes. The resulting allelic frequencies were compared with Ensembls database for surrounding populations to Myanmar and America. RESULTS The frequency of OPRM1, CYP2D6, SLCO1B1, MTHFR and VKORC1 were approximately 20% different in the Burmese refugee population as compared with the Ensembl populations. CONCLUSION Our study demonstrates that genetic differences are expected to affect drug efficacy in patients with a Burmese background.

Impact of training and student self-identification on frequency, constructiveness, and professionalism of pharmacy student evaluations of teaching

INTRODUCTION The purpose of this study was to simultaneously assess impact of enhanced training and anonymity on frequency, constructiveness, and professionalism of open-ended comments provided on course and instructor evaluations. METHODS In a 2 × 2 factorial study, didactic students at one doctor of pharmacy program were randomized to receive enhanced training in providing constructive feedback on student evaluations of teaching or an unrelated control activity at the beginning of the academic year, and to provide or not provide an electronic signature at the time of evaluation completion for two consecutive semesters. After ensuring intercoder reliability and agreement among all investigators, one external investigator coded all open-ended comments based on the following factors: comment provided/comment not provided, constructive/less than constructive, professional/unprofessional, training/no training, and signed/unsigned. RESULTS Of 836 opportunities to respond to open-ended items, 646 (77.3%) written comments were provided, which was similar by training (76.6% vs. 78.0%, p = 0.631) and signature (76.1% vs. 78.5%, p = 0.401) status. Of the 646 comments, 85.1% (n = 550) were constructive and 98.0% (n = 633) were professional. Students in the untrained/signed group were associated with decreased constructiveness (78.3%, OR 0.43, 95% CI 0.25-0.76, p = 0.003); overall, training was associated with increased constructiveness (88.3%, OR 1.70, 95% CI 1.09-2.65, p = 0.019). No factors were negatively or positively associated with professionalism when accounting for covariates. DISCUSSION Most students provided comments on course and instructor evaluations; most were constructive and professional. CONCLUSION Study group assignment did not substantially impact comment frequency or professionalism. Assignment to enhanced training, regardless of signature status, significantly increased constructiveness.