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Conference Paper: Mycophenolic acid pharmacokinetics and pharmacogenomics in lupus nephritis patients on maintenance immunosuppression
Title | Mycophenolic acid pharmacokinetics and pharmacogenomics in lupus nephritis patients on maintenance immunosuppression |
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Authors | |
Issue Date | 2017 |
Publisher | Oxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/ |
Citation | 54th European Renal Association & European Dialysis and Transplant Association Congress (ERA-EDTA), Madrid, Spain, 3-6 June 2017. In Nephrology Dialysis Transplantation, 2017, v. 32 n. Suppl. 3, p. iii506 How to Cite? |
Abstract | INTRODUCTION AND AIMS: There is little data on mycophenolic acid (MPA) pharmacokinetics and pharmacogenomics in lupus nephritis (LN) patients on long-term maintenance immunosuppression.
METHODS: Blood MPA level at 1, 2, 4, 8, 10 and 12 hours post-dose (i.e. C1, C2, C4, C8, C10 and C12) was measured in clinically stable LN patients receiving maintenance prednisolone and MMF, and repeated every 6 months. The relationship between MPA exposure and single nucleotide polymorphisms (SNP) related to the ATP Binding Subfamily C Member 2 (ABCC2) (rs2273697, rs3740066, rs717620 and rs17222723), organic anion transporting polypeptides (OATP) (rs7311358 and rs4149117) and uridine diphosphate glucuronosyltransferase (UGT) (rs17863762, rs6714486, rs17868320 and rs72551330) was investigated.
RESULTS: Seventy-three LN patients receiving prednisolone (6.8±2.4 mg/D) and MMF (1151.5±501.7 mg/D) were included. C1, C2 and C12 MPA levels were 9.4±8.1 mg/L, 8.1±5.9 mg/L and 2.1±1.7 mg/L respectively, and all correlated with AUC0-12 (r= r=0.521, 0.852 and 0.765, p=0.004, <0.001 and <0.001 respectively). C12 level inversely correlated with hemoglobin, total immunoglobulin, IgG, IgA and IgM levels, and leukocyte and platelet counts (p<0.05, for all). Four episodes of disease flares occurred during 17.8±7.3 months of follow-up, giving a relapse rate of 1 in 320 patient-months. C12 MPA levels were similar between relapse and non-relapse patients (2.1±0.9 mg/L vs. 2.4±1.2 mg/L, p=0.738). Higher MPA C12 levels were associated with anaemia (2.9±1.5 mg/L and 1.7±1.1 mg/L in patients with haemoglobin below or >10 g/dL respectively, p=0.003). MPA exposure was not related to infection (n=2) or gastrointestinal upset (n=3). SNP rs2273697 G/G in the ABCC2 gene was associated with higher MPA exposure (1891.5±918.9 mghL-1/gkg-1 vs. 1075.9±239.9 mghL-1/gkg-1, p=0.003) and lower total lymphocyte count (1.6±0.8 vs. 2.1±0.2 109/mL, p=0.01) compared with A/G genotype. SNPs of OATP and UGT were not related to MPA exposure.
CONCLUSIONS: C12 MPA level correlated with AUC0-12 and is related to haematological parameters and immunoglobulin suppression. SNP rs2273697 G/G genotype of the ABCC2 gene is associated with higher MPA exposure and lymphopenia. |
Description | Poster Session: Glomerulonephritis II, Poster no. MP216 |
Persistent Identifier | http://hdl.handle.net/10722/260765 |
ISSN | 2023 Impact Factor: 4.8 2023 SCImago Journal Rankings: 1.414 |
DC Field | Value | Language |
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dc.contributor.author | Yap, YHD | - |
dc.contributor.author | Yung, S | - |
dc.contributor.author | Tam, CH | - |
dc.contributor.author | Wong, S | - |
dc.contributor.author | Chan, DTM | - |
dc.date.accessioned | 2018-09-14T08:47:01Z | - |
dc.date.available | 2018-09-14T08:47:01Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | 54th European Renal Association & European Dialysis and Transplant Association Congress (ERA-EDTA), Madrid, Spain, 3-6 June 2017. In Nephrology Dialysis Transplantation, 2017, v. 32 n. Suppl. 3, p. iii506 | - |
dc.identifier.issn | 0931-0509 | - |
dc.identifier.uri | http://hdl.handle.net/10722/260765 | - |
dc.description | Poster Session: Glomerulonephritis II, Poster no. MP216 | - |
dc.description.abstract | INTRODUCTION AND AIMS: There is little data on mycophenolic acid (MPA) pharmacokinetics and pharmacogenomics in lupus nephritis (LN) patients on long-term maintenance immunosuppression. METHODS: Blood MPA level at 1, 2, 4, 8, 10 and 12 hours post-dose (i.e. C1, C2, C4, C8, C10 and C12) was measured in clinically stable LN patients receiving maintenance prednisolone and MMF, and repeated every 6 months. The relationship between MPA exposure and single nucleotide polymorphisms (SNP) related to the ATP Binding Subfamily C Member 2 (ABCC2) (rs2273697, rs3740066, rs717620 and rs17222723), organic anion transporting polypeptides (OATP) (rs7311358 and rs4149117) and uridine diphosphate glucuronosyltransferase (UGT) (rs17863762, rs6714486, rs17868320 and rs72551330) was investigated. RESULTS: Seventy-three LN patients receiving prednisolone (6.8±2.4 mg/D) and MMF (1151.5±501.7 mg/D) were included. C1, C2 and C12 MPA levels were 9.4±8.1 mg/L, 8.1±5.9 mg/L and 2.1±1.7 mg/L respectively, and all correlated with AUC0-12 (r= r=0.521, 0.852 and 0.765, p=0.004, <0.001 and <0.001 respectively). C12 level inversely correlated with hemoglobin, total immunoglobulin, IgG, IgA and IgM levels, and leukocyte and platelet counts (p<0.05, for all). Four episodes of disease flares occurred during 17.8±7.3 months of follow-up, giving a relapse rate of 1 in 320 patient-months. C12 MPA levels were similar between relapse and non-relapse patients (2.1±0.9 mg/L vs. 2.4±1.2 mg/L, p=0.738). Higher MPA C12 levels were associated with anaemia (2.9±1.5 mg/L and 1.7±1.1 mg/L in patients with haemoglobin below or >10 g/dL respectively, p=0.003). MPA exposure was not related to infection (n=2) or gastrointestinal upset (n=3). SNP rs2273697 G/G in the ABCC2 gene was associated with higher MPA exposure (1891.5±918.9 mghL-1/gkg-1 vs. 1075.9±239.9 mghL-1/gkg-1, p=0.003) and lower total lymphocyte count (1.6±0.8 vs. 2.1±0.2 109/mL, p=0.01) compared with A/G genotype. SNPs of OATP and UGT were not related to MPA exposure. CONCLUSIONS: C12 MPA level correlated with AUC0-12 and is related to haematological parameters and immunoglobulin suppression. SNP rs2273697 G/G genotype of the ABCC2 gene is associated with higher MPA exposure and lymphopenia. | - |
dc.language | eng | - |
dc.publisher | Oxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/ | - |
dc.relation.ispartof | Nephrology Dialysis Transplantation | - |
dc.relation.ispartof | 54th ERA-EDTA Congress | - |
dc.title | Mycophenolic acid pharmacokinetics and pharmacogenomics in lupus nephritis patients on maintenance immunosuppression | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Yap, YHD: desmondy@hku.hk | - |
dc.identifier.email | Yung, S: ssyyung@hku.hk | - |
dc.identifier.email | Chan, DTM: dtmchan@hkucc.hku.hk | - |
dc.identifier.authority | Yap, YHD=rp01607 | - |
dc.identifier.authority | Yung, S=rp00455 | - |
dc.identifier.authority | Chan, DTM=rp00394 | - |
dc.identifier.doi | 10.1093/ndt/gfx165.MP216 | - |
dc.identifier.hkuros | 290809 | - |
dc.identifier.volume | 32 | - |
dc.identifier.issue | Suppl. 3 | - |
dc.identifier.spage | iii506 | - |
dc.identifier.epage | iii506 | - |
dc.publisher.place | United Kingdom | - |
dc.identifier.issnl | 0931-0509 | - |