Pharmacokinetics of mycophenolic acid administered 3 times daily after hematopoietic stem cell transplantation with reduced-intensity regimen.
Mycophenolate mofetil (MMF) is an immunosuppressive drug used as a prophylactic agent to prevent acute graft-versus-host disease (aGVHD) after hematopoietic stem cell transplantation (HSCT). After reduced-intensity conditioning (RIC) regimen, administration of MMF orally 3 times a day (tid) seems to be more beneficial than twice a day (bid). However, information regarding the pharmacokinetic (PK) parameters of mycophenolic acid (MPA), the active metabolite of MMF, administered in this regimen are very limited. We performed a prospective study in 15 patients for whom 3 sets of sampling were performed: at the beginning of the treatment, after 1 week, and after 1 month. Two consecutive 8-hour sets of sampling were performed at day 0 (D0) and D7. Plasma concentrations of MPA were quantified and areas under the curve for 8hours (AUC(0-8)), and maximal and through concentrations were calculated. The results show that AUC(0-8) increases between the beginning of treatment and the end of the first week, but remains stable thereafter. Moreover, a trend to lower AUC(0-8) was observed for the patients who experienced GVHD > or =2 compared to those patients who did not. The other PK parameters are not associated with pharmacodynamic events. A limited sampling strategy with Bayesian estimators is currently under investigation to confirm these data and the role of D7 AUC(0-8) as a potential target of therapeutic drug monitoring (TDM).
Royer
Bernard
B
Inserm, U645, Besançon, France.
Larosa
Fabrice
F
Legrand
Faezeh
F
Gerritsen-van Schieveen
Pauline
P
Bérard
Michel
M
Kantelip
Jean-Pierre
JP
Deconinck
Eric
E
D000328:Adult; D004334:Drug Administration Schedule; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011446:Prospective Studies; D055815:Young Adult
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid