Abstract

The cytochrome P450 subfamily is comprised of three proteins CYP3A4, CYP3A5, and CYP3A7 which have been characterized. CYP3A4 is expressed in a majority of adult livers. In addition, CYP3A subfamily members have been identified in enterocytes and contribute to the first pass metabolism of CYP3A substrates. The antituberculosis agent, rifampin, is a potent inducer of CYP3A. Age and gender related differences in the extent of enzyme induction in animals and humans have been observed. Intestinal CYP3A plays an important role in the oral bioavailability of CYP3A substrates such as midazolam, nifedipine, and cyclosporine A. Midazolam is a 1,4 imidazobenzodiazepine which is a selective CYP3A subfamily member substrate and is currently employed as an in vivo probe for CYP3A hepatic and intestinal activity. The goals of this study are 1) to determine if elderly individuals have a decreased response to induction compared to young individuals 2) to determine if there are gender differences in the response to induction in elderly and young volunteers, and 3) to determine rifampin's principal site of induction using the simultaneous intravenous and oral administration of midazolam and a stable isotope.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
2M01RR000750-28
Application #
6307297
Study Section
Project Start
1999-12-01
Project End
2000-11-30
Budget Start
Budget End
Support Year
28
Fiscal Year
2000
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

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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
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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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