Page 1 |
Save page Remove page | Previous | 1 of 55 | Next |
|
small (250x250 max)
medium (500x500 max)
Large (1000x1000 max)
Extra Large
large ( > 500x500)
Full Resolution
All (PDF)
|
This page
All
|
THE PHARMACOKINETICS AND PHARMACODYNAMICS OF VINCRISTINE IN
THE ADOLESCENT AND YOUNG ADULT POPULATION COMPARED TO
YOUNGER PATIENTS
by
Leidy L. Isenalumhe
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(CLINICAL AND BIOMEDICAL INVESTIGATIONS)
AUGUST 2015
Copyright 2015 Leidy L. Isenalumhe
Object Description
| Title | The pharmacokinetics and pharmacodynamics of vincristine in the adolescent and young adult population compared to younger patients |
| Author | Isenalumhe, Leidy L. |
| Author email | sorianoleidy@gmail.com;Lisenalumhe@gmail.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Clinical and Biomedical Investigations |
| School | Keck School of Medicine |
| Date defended/completed | 2015-07-31 |
| Date submitted | 2015-07-31 |
| Date approved | 2015-08-03 |
| Restricted until | 2016-07-31 |
| Date published | 2016-07-31 |
| Advisor (committee chair) | Freyer, David |
| Advisor (committee member) |
Neely, Michael J. Azen, Stanley P. |
| Abstract | Improvement in survival from many forms of cancer among the adolescent and young adult (AYA) population has lagged behind that of younger patients. One contributing factor may be differences in tolerance of cancer treatments that lead to reduced adherence and efficacy. It has been shown that the AYA population has an increased prevalence of vincristine related neuropathy (VRNT), where dosage attenuation and/or increasing the dosing intervals which may decrease their cancer survival and reduced quality of life. Previous studies evaluated the relationship of age and vincristine pharmacokinetics (PK) have resulted in conflicting conclusions. These studies demarcated the AYA population as >10 years of age, which not only included adolescents and young adults, but also young children and pre-adolescent children. The proper characterization of this age group is critical, since developmental changes, as characterized by the Tanner staging, are associated with physiological variation that could significantly affect drug distribution and metabolism. Additionally, there are currently no means for predicting VRNT in any patient, regardless of age. ❧ We hypothesize that the pharmacokinetics/pharmacodynamics of vincristine differs between AYA and younger children, which may contribute to the excess VRNT found in the AYA population. One of our aims is to show that the PK of vincristine and its metabolite M1 will differ between young children and AYA as defined by Tanner stage. This is a novel way to define AYA compared with previously published VCR PK studies. Additionally, we hypothesize that calpain, a calcium-dependent protease that is believed to be associated with calcium mediated cell injury in the nervous system can serve as a biomarker predicting for VRNT in this age group. Hence, compared to baseline, serum calpain will increase after administration of vincristine. Changes in serum calpain, particularly if correlated with vincristine and/or M1 PK, would support further study of calpain as a biomarker of VRNT. |
| Keyword | AYA; adolescent and young adults; VCR; vincristine; VRNT; vincristine related neuropathy; ALL; acute lymphoblastic leukemia |
| Language | English |
| Format (imt) | application/pdf |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Contributing entity | University of Southern California |
| Rights | Isenalumhe, Leidy L. |
| Physical access | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@lib.usc.edu |
| Filename | etd-Isenalumhe-3786.pdf |
| Archival file | Volume4/etd-Isenalumhe-3786.pdf |
Description
| Title | Page 1 |
| Repository email | cisadmin@lib.usc.edu |
| Full text | THE PHARMACOKINETICS AND PHARMACODYNAMICS OF VINCRISTINE IN THE ADOLESCENT AND YOUNG ADULT POPULATION COMPARED TO YOUNGER PATIENTS by Leidy L. Isenalumhe A Thesis Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (CLINICAL AND BIOMEDICAL INVESTIGATIONS) AUGUST 2015 Copyright 2015 Leidy L. Isenalumhe |
