Abstract

The cytochrome P450 3 A subfamily is comprisd of four genes CYP3A3, CYP3A4, CYP3A5, and CYP3A7; with CYP3A4 expressed in a majority of adult livers. Recently, CYP3A4 has been identified in enterocytes. Thus, intestinal CYP3A may play an important role in the oral bioabailability of CYP3A substrates such as midazolam, nifedipine,a nd cyclosporine A. Midazolam is a 1,4 imidazobenzodiazepine that exhibits a lower than expected oral bioavailability assuming that the liver is the sole organ of metabolism. A goal of this study is to determine the contribution of intestinal cytochrome P450 3A to the observed first pass metabolism of midazolam following oral administration using simultaneous intravenous and oral administration of midazolam and a stable isotope. A second goal of the study is to determine if clarithromycin inhibits the metabolism following oral administation at the intestinal or hepatic level.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000750-26
Application #
6278994
Study Section
Project Start
1997-12-01
Project End
1998-11-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
26
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Indiana University-Purdue University at Indianapolis
Department
Type
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202

  Publications

Robinson-Cohen, Cassianne; Bartz, Traci M; Lai, Dongbing et al. (2018) Genetic Variants Associated with Circulating Fibroblast Growth Factor 23. J Am Soc Nephrol 29:2583-2592
Askie, Lisa M; Darlow, Brian A; Finer, Neil et al. (2018) Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA 319:2190-2201
Kadakia, Kunal C; Kidwell, Kelley M; Seewald, Nicholas J et al. (2017) Prospective assessment of patient-reported outcomes and estradiol and drug concentrations in patients experiencing toxicity from adjuvant aromatase inhibitors. Breast Cancer Res Treat 164:411-419
Criado, Kristen K; Sharp, William G; McCracken, Courtney E et al. (2017) Overweight and obese status in children with autism spectrum disorder and disruptive behavior. Autism :1362361316683888
Denson, Lee A; McDonald, Scott A; Das, Abhik et al. (2017) Early Elevation in Interleukin-6 is Associated with Reduced Growth in Extremely Low Birth Weight Infants. Am J Perinatol 34:240-247
Zillikens, M Carola; Demissie, Serkalem; Hsu, Yi-Hsiang et al. (2017) Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. Nat Commun 8:80
James, Jennifer; Munson, David; DeMauro, Sara B et al. (2017) Outcomes of Preterm Infants following Discussions about Withdrawal or Withholding of Life Support. J Pediatr 190:118-123.e4
Younge, Noelle; Goldstein, Ricki F; Bann, Carla M et al. (2017) Survival and Neurodevelopmental Outcomes among Periviable Infants. N Engl J Med 376:617-628
Srinivasan, Lakshmi; Page, Grier; Kirpalani, Haresh et al. (2017) Genome-wide association study of sepsis in extremely premature infants. Arch Dis Child Fetal Neonatal Ed 102:F439-F445
Gupta, Samir K; Yeh, Eunice; Kitch, Douglas W et al. (2017) Bone mineral density reductions after tenofovir disoproxil fumarate initiation and changes in phosphaturia: a secondary analysis of ACTG A5224s. J Antimicrob Chemother 72:2042-2048

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