• Evaluation of a Novel Charcoal Cookie Formulation for Drug Adsorption

      Klein-Schwartz, Wendy; Doyon, Suzanne; Dowling, Thomas C. (2010-09)
      Study Objectives: To determine the relative effect of a new charcoal cookie formulation on the absorption of orally administered cimetidine compared to a standard aqueous charcoal product; to compare the relative palatability of the two products. Design: Prospective, open-label, three-way cross-over trial Setting: General Clinical Research Center at University of Maryland Medical Center Patients: 8 healthy volunteers (ages 18 to 35 years of age). Intervention: After an overnight fast, subjects ingested cimetidine 800 mg tablet. At 15 minutes after the cimetidine dose subjects ingested either water, 3 charcoal cookies (equivalent to 7.2 g charcoal) or 7.2 g of aqueous activated charcoal suspension. Measurements: Venous blood samples were obtained over an 8 hour period for noncompartmental pharmacokinetic analysis including AUC and Cmax. Subjects evaluated the palatability of each product using a visual analog scale (VAS). Main Results: Both charcoal products effectively adsorbed cimetidine resulting in decreased absorption of most of the cimetidine dose. There was no difference in median percent decrease in cimetidine AUC (mg*hr/L) for the charcoal suspension and charcoal cookie [91.8% vs 82.1%] (p=0.505]. Similarly, there was no difference in the median percent decrease in Cmax (mg/L) for the charcoal suspension and charcoal cookies [82.6% vs 64.0%] (p=0.574). The palatability taste scores on VAS were 2.32 ±0.83 for the charcoal cookie and 1.08 ± 0.70 for the charcoal suspension. There was a significant difference in the palatability scores (p=0.001). All products were well tolerated and there were no adverse events reported. Conclusions: A new charcoal cookie formulation is as effective as the aqueous charcoal suspension at reducing absorption of cimetidine. The charcoal cookie is more palatable than the aqueous charcoal suspension.
    • Use of the Cockcroft-Gault versus the MDRD Study Equation to Dose Medications: An Opinion of the Nephrology Practice and Research Network of the American College of Clinical Pharmacy

      Nyman, Heather A.; Dowling, Thomas C.; Hudson, Joanna Q.; St. Peter, Wendy L.; Joy, Melanie S.; Nolin, Thomas D. (2011)
      Accurate assessment of kidney function is an important component of determining appropriate medication dosing regimens. Nearly all manufacturer-recommended dose adjustments are based on creatinine clearance ranges derived from clinical pharmacokinetic studies performed during the drug development process. The Cockcroft-Gault (C-G) equation provides an estimate of creatinine clearance and is the equation most commonly used to determine drug doses in patients with impaired kidney function. Recently, the Modification of Diet in Renal Disease Study (MDRD) equation has also been proposed for this purpose. Published studies report that drug doses determined by the two equations do not agree in 10-40% of cases. However, interpretation and comparison of these studies is complicated by the variable creatinine methods used for calculating C-G and MDRD estimates, the patient populations studied, and a lack of outcomes data demonstrating the clinical significance of dosing discrepancies. Moreover, the impact of reporting standardized serum creatinine values on the accuracy of the C-G equation and corresponding drug dosing regimens have been questioned. Currently, no prospective pharmacokinetic studies have been conducted using the MDRD equation to generate dosing recommendations, and limited data are available to support its use in some patient populations representing demographic extremes. Collectively, these issues have resulted in considerable confusion among clinicians and have fueled a healthy debate on whether or not to use the MDRD equation to dose medications. Each of these issues is reviewed, and a proposed algorithm for using creatinine-based kidney function assessments in medication dosing is provided. Knowledge of the advantages, limitations, and clinical role of each equation will facilitate their safe and effective use in medication dosing.
    • Dofetilide Dose Calculation Errors in Elderly Associated with Use of the Modification of Diet in Renal Disease Equation

      Denetclaw, Tina H.; Oshima, Nancy; Dowling, Thomas C. (2011)
      OBJECTIVE: To report 2 cases of drug dosage calculation errors that occurred when the Modification of Diet in Renal Disease (MDRD) equation was used for initiating drug therapy with dofetilide in elder~ patients with chronic kidney disease. CASE SUMMARY: An 83-year-old woman and a 92-year-old man were admitted for dofetilide treatment initiation and cardioversion for atrial fibrillation. The estimated glomerular filtration rate (eGFR) determined with use of the MDRD equation was significantly higher than the estimated creatinine clearance (eCrCl) determined with use of the Cockcroft-Gauf equation for both cases (85 vs 43 mUmin forthe man and 40 vs 24 mUmin for the woman). Initial dofetilide dosages calculated by the MDRD equation were 2-fold higher than those calculated by eCrCl in both cases. Initiation of dose based on the MDRD in the first patient led to a 32% increase in the QTc interval from baseline. Dofetilide therapy was adjusted for QTc interval prolongation based on eCrCl and reinitiated at a lower dose, and the patient did not develop further significant increases in the QTc interval. In the second patient, the lower dose based on eCrCl was initiated and the QTc interval remained within an acceptable range. DISCUSSION: The initial dosing of dofetilide is based on eCrCI as specified by the drug manufacturer. Recent widespread use and automated reporting of the eGFR by clinical laboratories has tempted some clinicians to consider using eGFR for calculating drug doses. However, recent data suggest that the eGFR, calculated by the MDRD equation, consistently overestimates eCrCI, leading to dose discrepancies, particularly in the elderly. The cases reported here illustrate the drug dose calculation errors that may occur when using the MDRD equation for initiating doses of dofetilide. CONCLUSIONS: Use of the eGFR or MDRD equation for calculation of doses in renal dysfunction has not been validated, and significant drug dose errors have been reported. The use of eGFR to calculate doses of dofetilide should be avoided.
    • Ready AND Willing: A Self-Assessment Tool to Determine Student Pharmacists' Confidence to Optimize Drug Therapy.

      Haines, Stuart T.; Lebovitz, Lisa; Roffman, David; Sturpe, Deborah A. (American College of Clinical Pharmacy Annual Meeting 2011, 2011)
    • Does an Integrated Curriculum Lead to Improved Confidence to Practice?

      Lebovitz, Lisa; Love, Raymond; Fu, Yunting; Dalby, Richard N. (2011-07)
    • Quantification of Acyclovir in Human Plasma by Ultra-High-Performance Liquid Chromatography - Heated Electrospray Ionization - Tandem Mass Spectrometry for Bioequivalence Evaluation

      Shao, Changxing; Dowling, Thomas C.; Haidar, Sam H.; Yu, L. X.; Polli, James E.; Kane, Maureen A. (2012)
      Pharmacokinetic studies are essential towards determining bioequivalence and establishing pharmacokinetic profiles for drug moieties requires accurate quantification. We report a rapid, sensitive, and robust method for the determination of acyclovir in human plasma and its validation towards evaluating the bioequivalence of drug formulations. After a simple liquid-liquid extraction from plasma, acyclovir is quantified using ultra-high-performance liquid chromatography - heated electrospray ionization - tandem mass spectrometry (UHPLC-HESI-MS/MS). The assay has a total analysis time is 5 min, a linear range of 1.0 - 2000 ng/mL, a lower limit of detection of 0.5 ng/ mL, and a lower limit of quantification of 1.0 ng/mL. Intra- and inter-day precision is no more than 10.3% and intraand inter-day accuracy was within 13% at various concentrations in human plasma. Validation according to FDA guidelines for bioanalysis indicates that the described UHPLC-HESI-MS/MS method provides rigorous quantification of acyclovir in human plasma and representative data demonstrates successful application towards the determination of pharmacokinetic profiles as part of an evaluation of drug formulation bioequivalence.
    • Building Partnerships: A Model for Collaborative Textbook Purchasing

      Douglas, C. Steven; Fu, Yunting; Tooey, M.J.; Lebovitz, Lisa (2012)
    • Student Time Allocation Practices vs. Academic Outcomes for Students From a Two-Campus Pharmacy School

      Congdon, Heather; Morgan, Jill A.; Lebovitz, Lisa (American Association of Colleges of Pharmacy Annual Meeting 2012, 2012-07)
    • Mapping as a Tool to Visualize and Quantify the Impact of Curricular Redesign

      Lebovitz, Lisa; Beardsley, Robert S. (American Association of Colleges of Pharmacy Annual Meeting 2012, 2012-07)
    • Population Pharmacokinetics and Pharmacodynamics of Ribavirin in Patients with Chronic Hepatitis C Genotype 1 Infection

      Jin, Runyan; Fossler, Michael James, Jr.; McHutchison, J. G.; Howell, Charles D.; Dowling, Thomas C. (2012-09)
      We report a population pharmacokinetic (PK) and pharmacodynamic (PD) model of orally administered ribavirin in patients with chronic hepatitis C virus (HCV) infection enrolled in a multicenter clinical trial, including the estimation of covariate effects on ribavirin PK parameters and sustained viral response (SVR). Ribavirin concentrations obtained from 144 patients, consisting of n=71 African American (AA) and n=73 Caucasian Americans (CA), during 24 weeks of therapy were best described by a twocompartment model with first-order absorption and elimination parameterized in terms of apparent oral clearance (CL/F), apparent central volume (Vc/F), apparent peripheral volume (Vp/F), and apparent intercompartmental clearance (Q/F). The typical population parameters were CL/F (19.0 L/h), Vc/F (1,130 L), Vp/F (4,020 L), andQ/F (38.6). The Vp/F was approximately 50% greater inAAcompared to CA. Significant covariates in the SVR model included IL-28B genotype, homeostasis model assessment of insulin resistance, and ribavirin exposure during the first week (AUC0−7). The population PK and logistic regression models both described the observed ribavirin concentration data and SVR data well. These findings suggest that optimization of ribavirin plasma concentrations during the first week of ribavirin dosing is most critical in AA patients in order to increase the rate of SVR, especially those with the IL-28B TT genotype.
    • Optimum ribavirin exposure overcomes racial disparity in efficacy of peginterferon and ribavirin treatment for hepatitis C genotype 1

      Jin, Runyan; Cai, Ling; McHutchison, J. G.; Dowling, Thomas C.; Howell, Charles D. (2012-11)
      OBJECTIVES: Peginterferon and ribavirin treatment is less effective for hepatitis C virus (HCV) genotype 1 infections in African Americans (AA) compared with Caucasian Americans (CA). Host genetic variability near the interleukin-28B (IL28B) gene locus is partly responsible. We investigated the relationship between ribavirin drug exposure and week 24 and 72 (sustained virologic response, SVR) responses (undetected serum HCV RNA) in 71 AA and 74 CA with HCV genotype 1 who received >90% of the prescribed peginterferon and weight-based ribavirin (1,000 or 1,200 mg per day) from week 1 to 24. METHODS: Ribavirin plasma levels were measured at weeks 1, 2, 4, 8, 12 and 24; ribavirin area under the concentration vs. time curve (AUC) was calculated using the linear trapezoidal rule. RESULTS: Compared with CA, AA had lower week 24 (WK24VR) (57.8 vs. 78.1; P<0.05) and week 72 (SVR) (36.6% vs 54.8%; P<0.05) response rates. AA also had significantly lower ribavirin exposure (AUC) from week 1 to 12 (P<0.05). Ribavirin exposures ≥4,065 and ≥4,480 ng/ml/day in the first week (AUC(0-7)) were thresholds for WK24VR and SVR in receiver-operating characteristic curve analyses. AA were less likely to have a threshold ribavirin AUC(0-7) level than CA (P<0.05). There were no significant racial differences in WK24VR (AA: 77 vs. CA: 84%) and SVR (AA: 52 vs. CA: 60%) rates in patients who met the ribavirin AUC(0-7) thresholds. Ribavirin AUC(0-7) predicted WK24VR and SVR independently of IL28B single-nucleotide polymorphism rs12979860 genotype. Yet, achieving threshold AUC(0-7) levels increased response rates primarily in AA with the less favorable non-C/C genotypes. CONCLUSIONS: Standard weight-based dosing leads to suboptimal ribavirin exposure in AA and contributes to the racial disparity in peginterferon and ribavirin treatment efficacy for HCV genotype 1.
    • Applied Pharmaceutical Sciences: An Innovative, Interdisciplinary Approach to Educating Both Students and Faculty

      Lebovitz, Lisa; Coop, Andrew; Rodriguez de Bittner, Magaly; Zuckerman, Ilene H. (2013)
      During the 2009 curricular redesign process, University of Maryland School of Pharmacy faculty members supported the concept that prior to embarking on advanced pharmacy practice experiences, students should know how to apply core knowledge and skills from the pharmaceutical, clinical and health services sciences to real world issues which arise in pharmacy practice and drug development, and be able to articulate and advocate for solutions to therapeutic dilemmas. The objective was to design a course that demonstrates integration and application of scientific principles to solve a therapeutic dilemma, and enhances interaction of faculty across disciplines.
    • Tracking Student Self-Confidence to Perform Curricular Outcome Tasks

      Haines, Stuart T.; Roffman, David; Sturpe, Deborah A.; Lebovitz, Lisa (American Association of Colleges of Pharmacy Annual Meeting 2013, 2013)
    • Novel Approach to an Assessment Committee

      Lebovitz, Lisa; Dalby, Richard N.; Shaya, Fadia T. (American Association of Colleges of Pharmacy Annual Meeting 2013, 2013-07)
    • Relationship between Student Confidence and Cumulative GPA Upon Completion of Didactic PharmD Coursework

      Lebovitz, Lisa; Haines, Stuart T.; Roffman, David; Sturpe, Deborah A.; Dalby, Richard N. (American Association of Colleges of Pharmacy Annual Meeting 2013, 2013-07)
    • Impact of New Didactic Curricular Design on Student Performance in APPEs

      Layson-Wolf, Cherokee; Lebovitz, Lisa (American Association of Colleges of Pharmacy Annual Meeting 2013, 2013-07)
    • A Flipped Model for MTM Core Elements in an IPPE

      Rocafort, Patrick Tim; Pincus, Kathleen J.; Lebovitz, Lisa; Brandt, Nicole J. (American Association of Colleges of Pharmacy Annual Meeting 2013, 2013-07)
    • Effects of Clonidine on Withdrawal from Long Term Dexmedetomidine in the Pediatric Patient

      Lardieri, Allison B.; Fusco, Nicholas; Simone, Shari; Morgan, Jill A.; Walker, L. Kyle; Parbuoni, Kristine A. (2013-12-19)
      Objectives: Primary Objective: To compare Withdrawal Assessment Tool-1 (WAT-1) scores among patients on clonidine to those not on clonidine, while being weaned from long term dexmedetomidine (≥5 days) Secondary Objective: To describe the withdrawal symptoms experienced after long term dexmedetomidine use (≥5 days)
    • Evaluation of the prevalence of delirium in a pediatric intensive care unit and the medications administered on delirium positive days

      Hutchins, Lisa; Lardieri, Allison B.; Morgan, Jill A.; Simone, Shari (2014-04-21)
      Objectives: The purpose of this study was to determine the prevalence of delirium in critically ill children and review the medications these patients received while positive for delirium.