Rita R. Alloway, PharmD, FCCP is the Director of Transplant Clinical Research for the University of Cincinnatiand a Research Professor of Medicine. Dr. Alloway, together with Drs Christians and Sander, will design,coordinate the study, design study database, analyze, interpret and publish the data. This is an open label,prospective, multicenter, randomized, replicate, six-period, six-sequence cross-over study to compare thesteady state pharmacokinetics of Prograf to Generic Hi to Generic Lo in stable renal (n=36) and liver transplant(n=36) subjects. The two generic products selected will be the most disparate generics as determined byevaluation of healthy volunteer ABE data along with product dissolution, potency, and impurity testing. Thetest products will be blinded by over encapsulation. The PK assessor will be blinded to the assigned treatmentsequence and formulation. The person analyzing the levels and analyzing the results will be blinded toformulation sequence. Dr. Alloway will interface with the University of Iowa Pharmaceuticals group forselection and preparation of final study product, and the University Hospital Investigational Drug Services tofacilitate timely study product availability to meet strict study timelines. In her role as PI, Dr. Alloway isresponsible for the overall study conduct. She will oversee the study conduct, data and sample collection,clarification of date entry, and compliant data handling. She will work with Drs. Shields, Kaiser, Woodle, Cardiand Sherman to facilitate study conduct by supervising the pharmacokinetic portion of the trial via adherenceassessments and time sampling compliance. She will interface with the Children's Medical Center group forproper analysis and collection of MEMS cap data during the study to quantitate patient adherence. From amanagement perspective, she will manage the research coordinator staff to assure proper study conduct whichwill include proper sample collection, handling and shipping subject samples to the University of Colorado foranalysis. Upon completion of tacrolimus level analysis, data will be provided to Dr. Sander Vinks for analysisof PK variables. In addition, Dr. Alloway will facilitate the interface with the CCTST and the coordinators inbuilding the study database in REDCap, coordinating efforts with the statisticians to assure proper datahandling, and completion of annual and final study reports/manuscripts.

Public Health Relevance

The proposed study and research strategy will systematically assess and challenge concerns that have been discussed in recent consensus papers, reviews and editorials related to bioequivalence testing for generic immunosuppressants. The results of this project may also be applicable to bioequivalence testing for other narrow therapeutic index drugs, ie antiepileptics, etc. However, the integration of these aspects is even more unique, will give a comprehensive picture, will reveal important new information and will provide a roadmap on how to address bioequivalence testing in narrow therapeutic index drugs in the future.

National Institute of Health (NIH)
Food and Drug Administration (FDA)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZFD1-SRC (99))
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University of Cincinnati
Internal Medicine/Medicine
Schools of Medicine
United States
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Shokati, Touraj; Bodenberger, Nicholas; Gadpaille, Holly et al. (2015) Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS. J Vis Exp :e52424