Mycophenolic acid exposure and complement fraction C3 influence inosine 5′-monophosphate dehydrogenase activity in systemic lupus erythematosus

• Published in: Annals of clinical biochemistry 2017-07, Vol.54 (4), p.490-494
• Main Authors: Mino, Yasuaki, Naito, Takafumi, Shimoyama, Kumiko, Ogawa, Noriyoshi, Kawakami, Junichi
• Format: Article
• Language: English
• Subjects: Adult; Body Weight; Complement C3 - metabolism; Cross-Sectional Studies; Drug Administration Schedule; Female; Glucuronides - blood; Glucuronides - pharmacokinetics; Humans; Immunosuppressive Agents - blood; Immunosuppressive Agents - pharmacokinetics; Immunosuppressive Agents - therapeutic use; IMP Dehydrogenase - antagonists & inhibitors; IMP Dehydrogenase - blood; Lupus Erythematosus, Systemic - drug therapy; Lupus Erythematosus, Systemic - enzymology; Lupus Erythematosus, Systemic - pathology; Male; Middle Aged; Multivariate Analysis; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - blood; Mycophenolic Acid - pharmacokinetics; Mycophenolic Acid - therapeutic use; Remission Induction; Ribonucleotides - blood
• ISSN: 0004-5632; 1758-1001
• DOI: 10.1177/0004563216667753

Background Mycophenolate mofetil has recently been reported to be effective against systemic lupus erythematosus. The influence of the pharmacokinetics of mycophenolic acid, the active form of mycophenolate mofetil and the major inactive mycophenolic acid phenolic glucuronide on the activity of the target enzyme inosine 5′-monophosphate dehydrogenase, is expected to be revealed. The aim of this study was to identify the factors associated with inosine 5′-monophosphate dehydrogenase activity in systemic lupus erythematosus patients. Methods Fifty systemic lupus erythematosus patients in remission maintenance phase (29 received mycophenolate mofetil [MMF+] and 21 did not [MMF−]) were enrolled. Median and interquartile range of dose of mycophenolate mofetil were 1500 and 1000–1500 mg/day, respectively. Stepwise multiple linear regression analysis was performed to assess the dependence between inosine 5′-monophosphate dehydrogenase activity and 25 predictor values including predose plasma concentrations of free mycophenolic acid and mycophenolic acid phenolic glucuronide. Results Median and interquartile range of predose total plasma concentrations of mycophenolic acid and mycophenolic acid phenolic glucuronide were 2.73 and 1.43–5.73 and 25.5 and 13.1–54.7 µg/mL, respectively. Predose inosine 5′-monophosphate dehydrogenase activity was significantly higher in MMF+ than MMF− patients (median 38.3 and 20.6 nmoL xanthosine 5′-monophosphate/g haemoglobin/h, P