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POSACONAZOLE PHARMACOKINETICS IN LUNG TRANSPLANT RECEIPIENTS WITH AND WITHOUT CYSTIC FIBROSIS

Zhang, Hongfei (2015) POSACONAZOLE PHARMACOKINETICS IN LUNG TRANSPLANT RECEIPIENTS WITH AND WITHOUT CYSTIC FIBROSIS. Master's Thesis, University of Pittsburgh. (Unpublished)

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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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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Zhang, Hongfeihoz24@pitt.eduHOZ24
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairVenkataramanan, Ramanrv@pitt.eduRV
Committee MemberBeumer, Janbeumerjh@upmc.eduJHB11
Committee MemberEnsor, Christopherensorcr2@upmc.edu
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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