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- Title
Higher exposure to mycophenolic acid with sirolimus than with cyclosporine cotreatment
- Authors
Büchler, Matthias; Lebranchu, Yvon; Bénéton, Maud; Le Meur, Yann; Heng, Anne Elisabeth; Westeel, Pierre François; le Guellec, Chantal; Libert, Frédéric; Hary, Lionel; Marquet, Pierre; Paintaud, Gilles
- Abstract
Introduction: Therapeutic drug monitoring of mycophenolate mofetil is recommended because of the interindividual variability in the exposition to its active moiety, mycophenolic acid. However, most of the pharmacokinetic studies involved patients cotreated with cyclosporine (INN, ciclosporin). Methods: We analyzed the pharmacokinetics of mycophenolic acid in 13 renal graft recipients treated with sirolimus in an anticalcineurin-free regimen and compared it with that of 17 patients cotreated with cyclosporine. The area under the concentration versus time curve over a 12-hour period (AUC0–12) of mycophenolic acid was estimated at 2 weeks, 1 month, 2 months, and 3 months after transplantation. Results: At the first 3 time points, patients cotreated with sirolimus had significantly higher mycophenolic acid AUC0–12 values compared with patients cotreated with cyclosporine, as follows: 81 mg·h/L (SD, 39 mg·h/L) versus 43 mg·h/L (SD, 11 mg·h/L) (P < .001), 72 mg·h/L (SD, 17 mg·h/L) versus 48 mg·h/L (SD, 13 mg·h/L) (P < .001), and 70 mg·h/L (SD, 25 mg·h/L) versus 47 mg·h/L (SD, 17 mg·h/L) (P < .01) at week 2, month 1, and month 2, respectively. At all time points, patients cotreated with sirolimus had significantly higher dose-normalized mycophenolic acid AUC0–12 values. At months 1 and 2, white blood cell counts were lower in the sirolimus group than in the cyclosporine group, as follows: 4.8 ×103/mL (SD, 1.1 ×103/mL) versus 6.5 ×103/mL (SD, 2.2 ×103/mL) (P < .01) at month 1 and 4.6 ×103/mL (SD, 1.1 ×103/mL) versus 5.9 ×103/mL (SD, 2.0 ×103/mL) (P < .05) at month 2. Conclusion: These data show that exposure to mycophenolic acid is higher in patients cotreated with sirolimus than in those cotreated with cyclosporine.
- Subjects
IMMUNOSUPPRESSIVE agents; PATIENT monitoring; IMMUNOPHARMACOLOGY; DRUG analysis
- Publication
Clinical Pharmacology & Therapeutics, 2005, Vol 78, Issue 1, p34
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1016/j.clpt.2005.03.005