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2015 ; 80
(5
): 1064-75
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Exposure-effect relationship of mycophenolic acid and prednisolone in adult
patients with lupus nephritis
#MMPMID25959850
Abd Rahman AN
; Tett SE
; Abdul Gafor HA
; McWhinney BC
; Staatz CE
Br J Clin Pharmacol
2015[Nov]; 80
(5
): 1064-75
PMID25959850
show ga
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 (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.
|Adult
[MESH]
|Dose-Response Relationship, Drug
[MESH]
|Drug Monitoring
[MESH]
|Drug Therapy, Combination
[MESH]
|Female
[MESH]
|Humans
[MESH]
|Immunosuppressive Agents/adverse effects/blood/*pharmacokinetics/*therapeutic use
[MESH]
|Lupus Nephritis/*drug therapy
[MESH]
|Male
[MESH]
|Middle Aged
[MESH]
|Mycophenolic Acid/adverse effects/blood/*pharmacokinetics/*therapeutic use
[MESH]
|Prednisolone/adverse effects/blood/*pharmacokinetics/*therapeutic use
[MESH]