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Dive into the research topics where Meagan J. Bemer is active.

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Featured researches published by Meagan J. Bemer.


Clinical Cancer Research | 2014

Busulfan in Infant to Adult Hematopoietic Cell Transplant Recipients: A Population Pharmacokinetic Model for Initial and Bayesian Dose Personalization

Jeannine S. McCune; Meagan J. Bemer; Jeffrey S. Barrett; K. Scott Baker; Alan S. Gamis; Nicholas H. G. Holford

Purpose: Personalizing intravenous busulfan doses to a target plasma concentration at steady state (Css) is an essential component of hematopoietic cell transplantation (HCT). We sought to develop a population pharmacokinetic model to predict i.v. busulfan doses over a wide age spectrum (0.1–66 years) that accounts for differences in age and body size. Experimental Design: A population pharmacokinetic model based on normal fat mass and maturation based on postmenstrual age was built from 12,380 busulfan concentration time points obtained after i.v. busulfan administration in 1,610 HCT recipients. Subsequently, simulation results of the initial dose necessary to achieve a target Css with this model were compared with pediatric-only models. Results: A two-compartment model with first-order elimination best fit the data. The population busulfan clearance was 12.4 L/h for an adult male with 62 kg normal fat mass (equivalent to 70 kg total body weight). Busulfan clearance, scaled to body size—specifically normal fat mass, is predicted to be 95% of the adult clearance at 2.5 years postnatal age. With a target Css of 770 ng/mL, a higher proportion of initial doses achieved the therapeutic window with this age- and size-dependent model (72%) compared with dosing recommended by the U.S. Food and Drug Administration (57%) or the European Medicines Agency (70%). Conclusion: This is the first population pharmacokinetic model developed to predict initial i.v. busulfan doses and personalize to a target Css over a wide age spectrum, ranging from infants to adults. Clin Cancer Res; 20(3); 754–63. ©2013 AACR.


The Journal of Clinical Pharmacology | 2013

Variation in Prescribing Patterns and Therapeutic Drug Monitoring of Intravenous Busulfan in Pediatric Hematopoietic Cell Transplant Recipients

Jeannine S. McCune; K. Scott Baker; David K. Blough; Alan S. Gamis; Meagan J. Bemer; Megan C. Kelton‐Rehkopf; Laura Winter; Jeffrey S. Barrett

Personalizing intravenous (IV) busulfan doses in children using therapeutic drug monitoring (TDM) is an integral component of hematopoietic cell transplant. The authors sought to characterize initial dosing and TDM of IV busulfan, along with factors associated with busulfan clearance, in 729 children who underwent busulfan TDM from December 2005 to December 2008. The initial IV busulfan dose in children weighing ≤12 kg ranged 4.8‐fold, with only 19% prescribed the package insert dose of 1.1 mg/kg. In those children weighing >12 kg, the initial dose ranged 5.4‐fold, and 79% were prescribed the package insert dose. The initial busulfan dose achieved the target exposure in only 24.3% of children. A wide range of busulfan exposures were targeted for children with the same disease (eg, 39 target busulfan exposures for the 264 children diagnosed with acute myeloid leukemia). Considerable heterogeneity exists regarding when TDM is conducted and the number of pharmacokinetic samples obtained. Busulfan clearance varied by age and dosing frequency but not by underlying disease. The authors— group is currently evaluating how using population pharmacokinetics to optimize initial busulfan dose and TDM (eg, limited sampling schedule in conjunction with maximum a posteriori Bayesian estimation) may affect clinical outcomes in children.


The Journal of Clinical Pharmacology | 2013

Population Pharmacokinetics and Dose Optimization of Mycophenolic Acid in HCT Recipients Receiving Oral Mycophenolate Mofetil

Hong Li; Donald E. Mager; D.G. Maloney; Meagan J. Bemer; Jeannine S. McCune

We sought to create a population pharmacokinetic model for total mycophenolic acid (MPA), to study the effects of different covariates on MPA pharmacokinetics, to create a limited sampling schedule (LSS) to characterize MPA exposure (i.e., area under the curve or AUC) with maximum a posteriori Bayesian estimation, and to simulate an optimized dosing scheme for allogeneic hematopoietic cell transplantation (HCT) recipients. Four thousand four hundred ninety‐six MPA concentration–time points from 408 HCT recipients were analyzed retrospectively using a nonlinear mixed effects modeling approach. MPA pharmacokinetics was characterized with a two‐compartment model with first‐order elimination and a time‐lagged first‐order absorption process. Concomitant cyclosporine and serum albumin were significant covariates. The median MPA clearance (CL) and volume of the central compartment were 24.2 L/hour and 36.4 L, respectively, for a 70 kg patient receiving tacrolimus with a serum albumin of 3.4 g/dL. Dosing simulations indicated that higher oral MMF doses are needed with concomitant cyclosporine, which increases MPA CL by 33.8%. The optimal LSS was immediately before and at 0.25 hours, 1.25 hours, 2 hours, and 4 hours after oral mycophenolate mofetil administration. MPA AUC in an individual HCT recipient can be accurately estimated using a five‐sample LSS and maximum a posteriori Bayesian estimation.


The Journal of Clinical Pharmacology | 2012

A limited sampling schedule to estimate mycophenolic Acid area under the concentration-time curve in hematopoietic cell transplantation recipients.

Hong Li; Donald E. Mager; Meagan J. Bemer; David H. Salinger; Paolo Vicini; Richard A. Nash; Jeannine S. McCune

Mycophenolate mofetil (MMF) is a key component of postgrafting immunosuppression in hematopoietic cell transplant (HCT) recipients. The plasma area under the curve (AUC) of its active metabolite, mycophenolic acid (MPA), is associated with MMF efficacy and toxicity. This study developed a population pharmacokinetic model of MPA in HCT recipients and created limited sampling schedules (LSSs) to enable individualized pharmacotherapy. A retrospective evaluation of MPA concentration‐time data following a 2‐hour MMF intravenous (IV) infusion was conducted in 77 HCT recipients. The final model consisted of 1 and 2 compartments for MMF and MPA pharmacokinetics, respectively. The mean estimated values (coefficient of variation, %) for total systemic clearance, distributional clearance, and central and peripheral compartment volumes of MPA were 36.9 L/h (34.5%), 15.3 L/h (80.4%), 11.9 L (71.7%), and 182 L (127%), respectively. No covariates significantly explained variability among individuals. Optimal LSSs were derived using a simulation approach based on the scaled mean squared error. A 5‐sample schedule of 2, 2.5, 3, 5, and 6 hours from the start of the infusion precisely estimated MPA AUC0‐12h for Q12‐hour IV MMF. A comparable schedule (2, 2.5, 3, 4, and 6 hours) similarly estimated MPA AUC0–8 h for Q8‐hour dosing.


Biology of Blood and Marrow Transplantation | 2013

Nonrelapse mortality and mycophenolic acid exposure in nonmyeloablative hematopoietic cell transplantation.

Cara L. McDermott; Barry E. Storer; Hong Li; Donald E. Mager; Michael Boeckh; Meagan J. Bemer; Jennifer A. Knutson; Jeannine S. McCune


Biology of Blood and Marrow Transplantation | 2014

Pharmacokinetic and Pharmacodynamic Analysis of Inosine Monophosphate Dehydrogenase Activity in Hematopoietic Cell Transplantation Recipients Treated with Mycophenolate Mofetil

Hong Li; Donald E. Mager; Barry E. Storer; Michael Boeckh; Meagan J. Bemer; Brian Phillips; Linda Risler; Jeannine S. McCune


Cancer Chemotherapy and Pharmacology | 2015

Association of fludarabine pharmacokinetic/dynamic biomarkers with donor chimerism in nonmyeloablative HCT recipients

Jeannine S. McCune; Donald E. Mager; Meagan J. Bemer; Barry E. Storer; Shelly Heimfeld


Cancer Chemotherapy and Pharmacology | 2013

A pilot pharmacologic biomarker study in HLA-haploidentical hematopoietic cell transplant recipients

Meagan J. Bemer; Mohamed L. Sorror; Paul V. O’Donnell; Jeannine S. McCune


Clinical Pharmacokinectics | 2016

Pharmacokinetics, Pharmacodynamics and Pharmacogenomics of Immunosuppressants in Allogeneic Haematopoietic Cell Transplantation: Part I

Jeannine S. McCune; Meagan J. Bemer


Biology of Blood and Marrow Transplantation | 2014

Recipient pretransplant inosine monophosphate dehydrogenase activity in nonmyeloablative hematopoietic cell transplantation.

Meagan J. Bemer; Linda Risler; Brian Phillips; Joanne Wang; Barry E. Storer; Haichuan Duan; Brianne S. Raccor; Michael Boeckh; Jeannine S. McCune

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Barry E. Storer

Fred Hutchinson Cancer Research Center

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Hong Li

University at Buffalo

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Michael Boeckh

Fred Hutchinson Cancer Research Center

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Alan S. Gamis

Children's Mercy Hospital

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Brian Phillips

University of Washington

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Jeffrey S. Barrett

Children's Hospital of Philadelphia

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K. Scott Baker

Fred Hutchinson Cancer Research Center

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Linda Risler

University of Washington

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