Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis

Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis

The aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis. METHODS: Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dos...

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Main Authors: Abd. Rahman, Nurul Azrin, Tett, Susan E., Abdul Gafor, Abdul Halim, McWhinney, Brett, Staatz, Christine E.
Format: Article
Language:English
Published: John Wiley & Sons, Inc. 2015
Subjects:
RM300 Drugs and their action
RS Pharmacy and materia medica
Online Access:http://irep.iium.edu.my/44995/
http://irep.iium.edu.my/44995/
http://irep.iium.edu.my/44995/
http://irep.iium.edu.my/44995/4/Rahman_et_al-2015-British_Journal_of_Clinical_Pharmacology.pdf
id iium-44995
recordtype eprints
spelling iium-449952017-08-10T04:03:04Z http://irep.iium.edu.my/44995/ Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis Abd. Rahman, Nurul Azrin Tett, Susan E. Abdul Gafor, Abdul Halim McWhinney, Brett Staatz, Christine E. RM300 Drugs and their action RS Pharmacy and materia medica The aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis. METHODS: Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C0 ), maximum concentration (Cmax ) and area under the concentration-time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drug-related adverse events. RESULTS: Dose-normalized AUC varied 10-, 8-, 7- and 19-fold for total MPA, unbound MPA, total prednisolone and unbound prednisolone, respectively. Median values (95% CI) of total MPA AUC(0,8 h) (21.5 [15.0, 42.0] vs. 11.2 [4.8, 30.0] mg l-1 h, P= 0.048) and Cmax (11.9 [6.7, 26.3] vs. 6.1 [1.6, 9.2] mg l-1 , P = 0.016) were significantly higher in responders than non-responders. Anaemia was significantly associated with higher total (37.8 [14.1, 77.5] vs. 18.5 [11.7, 32.7] mg l-1 h, P = 0.038) and unbound MPA AUC(0,12 h) (751 [214, 830] vs. 227 [151, 389] mg l-1 h, P = 0.004). Unbound prednisolone AUC(0,24 h) was significantly higher in patients with Cushingoid appearance (unbound: 1372 [1242, 1774] vs. 846 [528, 1049] nmol l-1 h, P = 0.019) than in those without. Poorer treatment response was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023). CONCLUSIONS: This study suggests a potential role for therapeutic drug monitoring in individualizing immunosuppressant therapy in patients with lupus nephritis. John Wiley & Sons, Inc. 2015-07-02 Article PeerReviewed application/pdf en http://irep.iium.edu.my/44995/4/Rahman_et_al-2015-British_Journal_of_Clinical_Pharmacology.pdf Abd. Rahman, Nurul Azrin and Tett, Susan E. and Abdul Gafor, Abdul Halim and McWhinney, Brett and Staatz, Christine E. (2015) Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis. British Journal of Clinical Pharmacology, 80 (5). pp. 1064-1075. ISSN 0306-5251 http://onlinelibrary.wiley.com/doi/10.1111/bcp.12678/abstract;jsessionid=AABBE5A02EE3E0C36FF879312BBDBB41.f02t03 10.1111/bcp.12678
repository_type Digital Repository
institution_category Local University
institution International Islamic University Malaysia
building IIUM Repository
collection Online Access
language English
topic RM300 Drugs and their action
RS Pharmacy and materia medica
spellingShingle RM300 Drugs and their action
RS Pharmacy and materia medica
Abd. Rahman, Nurul Azrin
Tett, Susan E.
Abdul Gafor, Abdul Halim
McWhinney, Brett
Staatz, Christine E.
Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis
description The aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis. METHODS: Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C0 ), maximum concentration (Cmax ) and area under the concentration-time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drug-related adverse events. RESULTS: Dose-normalized AUC varied 10-, 8-, 7- and 19-fold for total MPA, unbound MPA, total prednisolone and unbound prednisolone, respectively. Median values (95% CI) of total MPA AUC(0,8 h) (21.5 [15.0, 42.0] vs. 11.2 [4.8, 30.0] mg l-1 h, P= 0.048) and Cmax (11.9 [6.7, 26.3] vs. 6.1 [1.6, 9.2] mg l-1 , P = 0.016) were significantly higher in responders than non-responders. Anaemia was significantly associated with higher total (37.8 [14.1, 77.5] vs. 18.5 [11.7, 32.7] mg l-1 h, P = 0.038) and unbound MPA AUC(0,12 h) (751 [214, 830] vs. 227 [151, 389] mg l-1 h, P = 0.004). Unbound prednisolone AUC(0,24 h) was significantly higher in patients with Cushingoid appearance (unbound: 1372 [1242, 1774] vs. 846 [528, 1049] nmol l-1 h, P = 0.019) than in those without. Poorer treatment response was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023). CONCLUSIONS: This study suggests a potential role for therapeutic drug monitoring in individualizing immunosuppressant therapy in patients with lupus nephritis.
format Article
author Abd. Rahman, Nurul Azrin
Tett, Susan E.
Abdul Gafor, Abdul Halim
McWhinney, Brett
Staatz, Christine E.
author_facet Abd. Rahman, Nurul Azrin
Tett, Susan E.
Abdul Gafor, Abdul Halim
McWhinney, Brett
Staatz, Christine E.
author_sort Abd. Rahman, Nurul Azrin
title Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis
title_short Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis
title_full Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis
title_fullStr Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis
title_full_unstemmed Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis
title_sort exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis
publisher John Wiley & Sons, Inc.
publishDate 2015
url http://irep.iium.edu.my/44995/
http://irep.iium.edu.my/44995/
http://irep.iium.edu.my/44995/
http://irep.iium.edu.my/44995/4/Rahman_et_al-2015-British_Journal_of_Clinical_Pharmacology.pdf
first_indexed 2023-09-18T21:03:59Z
last_indexed 2023-09-18T21:03:59Z
_version_ 1777410810522370048

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