Pamala Jacobson, Pharm.D. is an Assistant Professor in the Department of Experimental and Clinical Pharmacology at the University of Minnesota (MN). She has 9 years of clinical experience in hematopoietic stem cell transplantation (HSCT) and now wishes to change her career focus to clinical research. Her long-termcareer goal is to become an independent investigator focusing on clinical pharmacology in HSCT. Her immediate goal is, to receive research training to prepare herself as an independently funded investigator. She proposes to conduct mentored clinical research under her mentors and complete the Clinical Research Masters Program, University of MN, The University of MN is home to one of the oldest and largest academically based HSCT programs in the world, a top-ranked College of Pharmacy and School of Public Health, and is well equipped to support the candidate. The program of study will focus on clinical trial design, biostatistics, ethics, pharmacokinetics and pharmacodynamics. The applicant's research will explore the pharmacokinetics of the immunosuppressant, mycophenolate, and the relationships between pharmacokinetics and clinical outcomes in nonmyeloablative allogeneic HSCT. Less toxic """"""""nonmyeloablative"""""""" preparative regimens, containing mycophenolate, are under investigation. These regimens use a standard, fixed dose of mycophenolate and are associated with variable immunosuppression and outcomes. We hypothesize that the variability in outcomes is related to differences in mycophenolate pharmacokinetics.
Specific Aim I will evaluate the relationships between mycophenolate pharmacokinetic measures and clinical endpoints.
Specific Aim II will assess pretransplant mycophenolate pharmacokinetics to determine inter-patient variability and identify covariates associated with their variability.
Specific Aim III will assess posttransplant pharmacokinetics to determine intra-patient variability and identify peritransplant events associated with variability. We anticipate that monitoring of mycophenolate concentrations and individualized dosing is warranted. The long-term goal of this research is to reduce the rates of graft vs. host disease, graft failure, toxicity and improve survival following nonmyeloablative HSCT. The overall goal is to provide the applicant with formal and comprehensive training as a clinical cancer investigator.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23CA096622-05
Application #
7075292
Study Section
Subcommittee G - Education (NCI)
Program Officer
Gorelic, Lester S
Project Start
2002-09-14
Project End
2007-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
5
Fiscal Year
2006
Total Cost
$127,318
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Johnson, L'Aurelle A; Malayappan, Bhaskar; Tretyakova, Natalia et al. (2012) Formation of cyclophosphamide specific DNA adducts in hematological diseases. Pediatr Blood Cancer 58:708-14
Long-Boyle, J R; Green, K G; Brunstein, C G et al. (2011) High fludarabine exposure and relationship with treatment-related mortality after nonmyeloablative hematopoietic cell transplantation. Bone Marrow Transplant 46:20-6
Jacobson, Pamala A; Huang, Jiayin; Wu, Juan et al. (2010) Mycophenolate pharmacokinetics and association with response to acute graft-versus-host disease treatment from the Blood and Marrow Transplant Clinical Trials Network. Biol Blood Marrow Transplant 16:421-9
Jacobson, P; El-Massah, S F; Rogosheske, J et al. (2009) Comparison of two mycophenolate mofetil dosing regimens after hematopoietic cell transplantation. Bone Marrow Transplant 44:113-20
Martin, Paul J; Storer, Barry E; Rowley, Scott D et al. (2009) Evaluation of mycophenolate mofetil for initial treatment of chronic graft-versus-host disease. Blood 113:5074-82
Jacobson, Pamala; Huang, Jaiyin; Rydholm, Nancy et al. (2008) Higher mycophenolate dose requirements in children undergoing hematopoietic cell transplant (HCT). J Clin Pharmacol 48:485-94
Huang, Jiayin; Jacobson, Pamala; Brundage, Richard (2007) Prediction of unbound mycophenolic acid concentrations in patients after hematopoietic cell transplantation. Ther Drug Monit 29:385-90
Ng, Juki; Rogosheske, John; Barker, Juliet et al. (2006) A limited sampling model for estimation of total and unbound mycophenolic acid (MPA) area under the curve (AUC) in hematopoietic cell transplantation (HCT). Ther Drug Monit 28:394-401
Jacobson, Pamala A; Green, Kathleen G; Hering, Bernhard J (2005) Mycophenolate mofetil in islet cell transplant: variable pharmacokinetics but good correlation between total and unbound concentrations. J Clin Pharmacol 45:901-9
Jacobson, Pamala; Rogosheske, John; Barker, Juliet N et al. (2005) Relationship of mycophenolic acid exposure to clinical outcome after hematopoietic cell transplantation. Clin Pharmacol Ther 78:486-500