alexa Docetaxel pharmacokinetics and its correlation with two in vivo probes for cytochrome P450 enzymes: the C(14)-erythromycin breath test and the antipyrine clearance test.
Pharmaceutical Sciences

Pharmaceutical Sciences

Clinical Pharmacology & Biopharmaceutics

Author(s): Michael M, Cullinane C, Hatzimihalis A, OKane C, Milner A,

Abstract Share this page

Abstract BACKGROUND: Docetaxel has marked inter-patient PK variability, and metabolic phenotypic probes may enable individualised dosing. This is the first report directly comparing the erythromycin breath test (EBT) (a CYP3A4 probe) with the antipyrine clearance test (ACT), (a general CYP-P450/predominant CYP3A4 probe) for the correlation with docetaxel PK and toxicity. METHODS: Patients pretherapy underwent: (A) EBT: IV C(14)[N-methyl]-erythromycin was administered and breath samples analysed for (14)CO(2), derived parameters included (1) (14)CO(2) flux at 10-min (CO(2)f(10)), (2) 20-min (CO(2)f(20)), (3) terminal rate constant k(CO2) and (4) AUC(CO2,(0-∞)) and AUC(CO2,(0-60).) (B) ACL test: patients were given oral antipyrine 10 mg/kg, blood samples were taken for PK, and the clearance (CL(Ant)) was derived. Docetaxel was then given at 75 mg/m(2)/3-weekly or 35 mg/m(2)/weekly. Samples taken for docetaxel PK in first course on day 1 and PK parameters included clearance (CL(Doc)). RESULTS: Twenty patients accrued, docetaxel: 3-weekly/weekly = 13:7. EBT parameters (N = 19) (mean, [CV\%]): CO(2)f(10) (\%/min) 0.051 (106), CO(2)f(20) 0.052 (82), k(CO2) (min(-1)) 0.007 (22), AUC(CO2,(0-∞)) 7.9 (85), AUC(CO2,(0-60)) 2.64 (81). CL(Ant) (N = 19) (ml/min); 35.8 (37). Docetaxel PK parameters (N = 19): CL(Doc) (l/h) = 57.2 (36), t(Doc1/2) (h) = 12.7 (33). No correlations were observed between the docetaxel PK and EBT parameters. For docetaxel weekly patients, a significant linear relationship was observed between CL(Doc) and CL(Ant) (P = 0.007, R (2) = 79.47\%). CONCLUSIONS: The utility of EBT for the prediction of docetaxel PK was not confirmed in this study. The antipyrine clearance test may be superior in this regard for docetaxel, but regimen dependent and hence warrants further evaluation. This article was published in Cancer Chemother Pharmacol and referenced in Clinical Pharmacology & Biopharmaceutics

Relevant Expert PPTs

Relevant Speaker PPTs

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords