Abstract

Tacrolimus (TAC) is a potent immunosuppressant used primarily for the prevention of allograft rejection in liver transplant. TAC is poorly and erratically absorbed after oral administration with its bioavailability averaging 25-30%. Interaction of TAC with p-glycoprotein and CYP3A may be the cause of the low and highly variable bioavailability of this agent. Studies from our lab and others have demonstrated that intestinal metabolism is an important determinant of tacrolimus bioavailability. This study is designed to demonstrate that intestinal p-glycoprotein plays a major role in the absorption and bioavailability of TAC. It will allow us to evaluate the extent to which administration of fluconazole, given orally or intravenously, affects the pharmacokinetics of TAC, with particular emphasis on possible differences in the effects of fluconazole on p-glycoprotein in both liver and gut. The GCRC facility will allow us to study our human subjects in an outpatient setting.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000079-38
Application #
6416983
Study Section
Project Start
2000-12-01
Project End
2001-11-30
Budget Start
Budget End
Support Year
38
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Kurtz, Theodore W; DiCarlo, Stephen E; Pravenec, Michal et al. (2018) Functional foods for augmenting nitric oxide activity and reducing the risk for salt-induced hypertension and cardiovascular disease in Japan. J Cardiol 72:42-49
Anderegg, Nanina; Johnson, Leigh F; Zaniewski, Elizabeth et al. (2017) All-cause mortality in HIV-positive adults starting combination antiretroviral therapy: correcting for loss to follow-up. AIDS 31 Suppl 1:S31-S40
Kurtz, Theodore W; DiCarlo, Stephen E; Morris Jr, R Curtis (2016) Logical Issues With the Pressure Natriuresis Theory of Chronic Hypertension. Am J Hypertens 29:1325-1331
Cruz, Giovanna I; Shao, Xiaorong; Quach, Hong et al. (2016) A Child's HLA-DRB1 genotype increases maternal risk of systemic lupus erythematosus. J Autoimmun 74:201-207
Morris Jr, R Curtis; Schmidlin, Olga; Sebastian, Anthony et al. (2016) Vasodysfunction That Involves Renal Vasodysfunction, Not Abnormally Increased Renal Retention of Sodium, Accounts for the Initiation of Salt-Induced Hypertension. Circulation 133:881-93
Kurtz, Theodore W; DiCarlo, Stephen E; Pravenec, Michal et al. (2016) An alternative hypothesis to the widely held view that renal excretion of sodium accounts for resistance to salt-induced hypertension. Kidney Int 90:965-973
Brambati, Simona Maria; Amici, Serena; Racine, Caroline A et al. (2015) Longitudinal gray matter contraction in three variants of primary progressive aphasia: A tenser-based morphometry study. Neuroimage Clin 8:345-55
Abraham, Alison G; Althoff, Keri N; Jing, Yuezhou et al. (2015) End-stage renal disease among HIV-infected adults in North America. Clin Infect Dis 60:941-9
Wang, Julie B; Pierce, John P; Ayala, Guadalupe X et al. (2015) Baseline Depressive Symptoms, Completion of Study Assessments, and Behavior Change in a Long-Term Dietary Intervention Among Breast Cancer Survivors. Ann Behav Med 49:819-27
Brehm, John M; Ramratnam, Sima K; Tse, Sze Man et al. (2015) Stress and Bronchodilator Response in Children with Asthma. Am J Respir Crit Care Med 192:47-56

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