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Exposure–effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis
Author(s) -
Abd Rahman Azrin N.,
Tett Susan E.,
Abdul Gafor Halim A.,
McWhinney Brett C.,
Staatz Christine E.
Publication year - 2015
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12678
Subject(s) - prednisolone , cmax , medicine , area under the curve , pharmacokinetics , lupus nephritis , gastroenterology , pharmacology , disease
Aims 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 ( C 0 ), maximum concentration ( C max ) 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 C max (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.