Alghazwani, Yahia
(2012)
REGULATION OF GLUCURONIDATION (UGT1A9) PATHWAY DURING PREGNANCY.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Pregnancy is associated with many physiological changes. During pregnancy, the pharmacokinetics of certain drugs are altered. In particular, the clearance of drugs undergoing glucuronidation has been reported to drastically increase during pregnancy. Pregnancy-mediated changes in the plasma concentrations of estrogens and progesterone have been suggested to influence the expression and activity of certain phase I metabolic enzymes. Limited information, however, is available on the effect of pregnancy-related hormones on the activity of glucuronide-conjugating enzymes in humans. In this study, we determined the optimal conditions for evaluating glucuronidation in human liver microsomal systems. We also determined the effects of progesterone and estradiol on the expression of UGT1A9 mRNA, and the activity UGT1A9 (formation of mycophenolic acid glucuronide (MPAG) from mycophenolic acid (MPA)) using primary cultures of human hepatocytes. The results showed a non-significant increase in the expression of UGT1A9 and in the formation of mycophenolic acid glucuronide from MPA in human hepatocytes treated with a combination of progesterone and estradiol. Progesterone and estradiol do not appear to significantly alter the metabolism of the substrates of UGT1A9. Future studies should evaluate additional factors that may account for the observed alterations in UGT1A9 activity during pregnancy.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Alghazwani, Yahia | ysa6@pitt.edu | YSA6 | |
|
| ETD Committee: |
| Title | Member | Email Address | Pitt Username | ORCID |
|---|
| Committee Chair | Venkataramanan, Raman | rv@pitt.edu | RV | | | Committee Member | Zemaitis, MA | maz@pitt.edu | MAZ | | | Committee Member | Vollmer, Regis R. | vollm@pitt.edu | VOLLM | |
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| Date: |
17 December 2012 |
| Date Type: |
Publication |
| Defense Date: |
23 April 2012 |
| Approval Date: |
17 December 2012 |
| Submission Date: |
15 December 2012 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
46 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Pharmacy > Pharmaceutical Sciences |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
UGT1A9, mycophenolic acid, mycophenolic acid glucuronide, estradiol, progesterone, pregnancy, glucuronidation |
| Date Deposited: |
17 Dec 2012 16:14 |
| Last Modified: |
15 Nov 2016 14:08 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/16992 |
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