Zhang, Hongfei
(2015)
POSACONAZOLE PHARMACOKINETICS IN LUNG TRANSPLANT RECEIPIENTS WITH AND WITHOUT CYSTIC FIBROSIS.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
The incidence of invasive fungal infections (IFIs) is significantly high in patients following lung transplantation. There have been no investigations on the pharmacokinetics of posaconazole in patients with CF. In this study, 7 patients with CF and 13 patients without CF were enrolled in a pharmacokinetic study upon initiation of posaconazole prophylaxis following lung transplantation. We established a sensitive HPLC-fluorescence assay method to measure plasma concentration of posaconazole. After a minimum five days of treatment, maximum plasma concentration Css, max (0.311 μg/mL) in CF patients was 56% lower compared to Css, max (0.699 μg/mL) in non-CF patients; the minimum plasma concentration Css, min (0.189·μg/mL) in CF patients was lower by 60% compared to Css, min (0.474 μg/mL) in non-CF patients; the average plasma concentration Css, av (0.233 μg/mL) in CF patients was lower by 61% compared to Css, av (0.594 μg/mL) in non-CF patients, the dose normalized plasma area under curve AUC0-24 (0.007 h*μg/mL) in CF patients was 65% lower compared to dose normalized AUC0-24 (0.02 h*μg/mL) in non-CF patients, and the apparent oral clearance of 2.51 L/h/kg in CF patients was 3.4 times higher compared to 0.74 L/h/kg in non-CF patients. Moreover, a steady state average concentration of 0.7 μg/mL that is considered to be essentials for prophylaxis was only achieved in 4 out of 20 patients. A good correlation between Ctrough and AUC0-τ demonstrates Ctrough is a good surrogate marker to monitor systemic exposure of posaconazole in LTRs.
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| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
30 July 2015 |
| Date Type: |
Publication |
| Defense Date: |
15 July 2015 |
| Approval Date: |
30 July 2015 |
| Submission Date: |
28 July 2015 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
50 |
| 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: |
posaconazole, pharmacokinetics, HPLC |
| Date Deposited: |
30 Jul 2015 15:00 |
| Last Modified: |
19 Dec 2016 14:42 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/25831 |
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