Pharmacokinetics and pharmacogenomics of mycophenolic acid and its clinical correlations in maintenance immunosuppression for lupus nephritis.
In: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal, Jg. 35 (2020-05-01), Heft 5, S. 810-818
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Zugriff:
Background: There is little data on mycophenolic acid (MPA) pharmacokinetics and pharmacogenomics and optimal MPA exposure in lupus nephritis (LN) patients during long-term maintenance.
Methods: We measured blood MPA levels at 1, 2, 4, 8, 10 and 12-h post-dose (i.e. C1, C2, C4, C8, C10 and C12) in 88 stable LN patients receiving maintenance prednisolone and mycophenolate mofetil, repeated every 6 months. The relationship between MPA exposure and single nucleotide polymorphisms (SNPs) of adenosine triphosphate-binding cassette subfamily C member 2 (ABCC2; rs2273697, rs3740066, rs717620 and rs17222723), organic anion-transporting polypeptides (OATPs; rs7311358 and rs4149117) and uridine diphosphate glucuronosyltransferase (UGT; rs17863762, rs6714486, rs17868320 and rs72551330) was also investigated.
Results: C1, C2 and C12 were 8.3 ± 6.6 , 7.2 ± 5.2 and 2.0 ± 1.4 mg/L and all correlated with the 12-h area under the curve (AUC0-12; r = 0.51, 0.85 and 0.73; P = 0.02, <0.001 and <0.001, respectively). C12 inversely correlated with hemoglobin, immunoglobulins and leukocyte levels (P < 0.05 for all). Five renal flares, 11 episodes of infection and 10 episodes of anemia (hemoglobin <10 g/dL) occurred over 96 weeks, with a corresponding C12 of 1.3 ± 0.5, 4.3 ± 2.6 and 2.9 ± 1.5 mg/L, respectively (versus 2.4 ± 1.2, 1.8 ± 1.2 and 1.7 ± 1.1 mg/L in patients without these complications; P = 0.041, <0.001 and 0.004). SNP rs2273697 A/G in the ABCC2 gene was associated with lower MPA exposure compared with G/G (1075.9 ± 239.9 versus 1891.5 ± 918.9 mgh/L per g/kg; P = 0.003). SNPs of OATP and UGT were unrelated to MPA level.
Conclusion: MPA C12 correlates with the AUC0-12 and is related to renal flare, infection and anemia. SNP rs2273697 A/G is associated with lower MPA exposure.
(© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)
| Titel: |
Pharmacokinetics and pharmacogenomics of mycophenolic acid and its clinical correlations in maintenance immunosuppression for lupus nephritis.
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| Autor/in / Beteiligte Person: | Yap, DYH ; Tam, CH ; Yung, S ; Wong, S ; Tang, CSO ; Mok, TMY ; Yuen, CKY ; Ma, MKM ; Lau, CS ; Chan, TM |
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| Zeitschrift: | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal, Jg. 35 (2020-05-01), Heft 5, S. 810-818 |
| Veröffentlichung: | Oxford : Oxford University Press ; <i>Original Publication</i>: [Berlin ; New York, NY] : Springer International, [c1986-, 2020 |
| Medientyp: | academicJournal |
| ISSN: | 1460-2385 (electronic) |
| DOI: | 10.1093/ndt/gfy284 |
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