David A Flockhart

US Patent:

20080085240, Apr 10, 2008

Filed:

Aug 31, 2007

Appl. No.:

11/848750

Inventors:

David Flockhart - Indianapolis IN, US
Zeruesenay Desta - Carmel IN, US
Anil S. Modak - Haverhill MA, US
Yasuhisa Kurogi - North Andover MA, US

International Classification:

A61K 51/04
G01N 33/00

US Classification:

424001810, 436133000

Abstract:

The present invention relates, generally to a method of determining and assessing cytochrome P450 2C19-related (CYP2Cl9) metabolic capacity in an individual mammalian subject via a breath assay, by determining the relative amount of COexhaled by the subject upon intravenous or oral administration of a C-labeled CYP2C19 substrate compound. The present invention is useful as a non-invasive, in vivo assay for evaluating CYP2C19 enzyme activity in a subject using the metabolite COin expired breath, to phenotype individual subjects and to determine the selection, optimal dosage and timing of drug administration.

US Patent:

20110111510, May 12, 2011

Filed:

Nov 9, 2010

Appl. No.:

12/942280

Inventors:

David A. Flockhart - Indianapolis IN, US
Zeruesenay Desta - Carmel IN, US
Anil S. Modak - Haverhill MA, US
Yasuhisa Kurogi - North Andover MA, US

International Classification:

G01N 37/00
C07D 401/12

US Classification:

436 56, 5462737

Abstract:

The present invention relates, generally to a method of determining and assessing cytochrome P450 2C19-related (CYP2C19) metabolic capacity in an individual mammalian subject via a breath assay, by determining the relative amount of COexhaled by the subject upon intravenous or oral administration of a C-labeled CYP2C19 substrate compound. The present invention is useful as anon-invasive, in vivo assay for evaluating CYP2C19 enzyme activity in a subject using the metabolite COin expired breath, to phenotype individual subjects and to determine the selection, optimal dosage and timing of drug administration.

US Patent:

20120088247, Apr 12, 2012

Filed:

Feb 23, 2010

Appl. No.:

13/202418

Inventors:

David Flockhart - Indianapolis IN, US
Zeruesenay Desta - Carmel IN, US
Anne Nguyen - Indianapolis IN, US
Todd Skaar - Carmel IN, US
Lang Li - Carmel IN, US

Assignee:

Indian University Research & Technology Corporatio - Indianapolis IN

International Classification:

C12Q 1/68

US Classification:

435 612

Abstract:

A pathway for the metabolism of tamoxifen is identified including the activity of at least 2 different isoforms of UGY2B7. This pathway includes isozymes of CYP3A which convert tamoxifen (TAM) to N-desmethyl-TAM, which is then converted to endoxifen by the action of CYP2D6. Once formed, endoxifen may be degraded by at least one isozyme of UGT2B7. Patients that have highly active isoforms of CYP2D6 and slow acting isoforms of UGT2B7 accumulate high levels of endoxifen and are good candidates for treatment with tamoxifen. Also disclosed are methods for screening patients with a high likelihood of benefiting from treatment with tamoxifen. These methods include testing patients for various alleles of genes known to be involved in tamoxifen metabolism and treating patients accordingly.