Dosing of MMF in combination with tacrolimus for steroid-resistant vascular rejection in pediatric renal allografts.

Steroid-resistant vascular rejection was treated in seven adolescent renal allograft recipients using the combination of mycophenolate mofetil (MMF) and tacrolimus (FK506). Since there are no published pediatric dose recommendations for MMF using this combination, trough concentrations and pharmacokinetic profiles were used for therapeutic drug monitoring. In order to keep the mycophenolic acid (MPA) concentrations between 2-5 micrograms/ml, mean MMF doses were reduced from 600 to 250 mg/m2 b.i.d. Apparent clearance of MPA decreased from 5 to 1 ml/min per kg within 2 weeks. Pharmacokinetic monitoring revealed substantial variability among patients of both MMF and FK506. The MPA dose ranged from 178 to 1008 mg/m2 per day to achieve an area under the curve (AUC) of 59.9 micrograms x h/ml +/- 10.5 SD (range 49-65 micrograms). FK506 dose ranged from 1.3 to 8.8 mg/m2 per day to achieve an AUC of 116 ng x h/ml +/- 27 SD (range 83-145). We recommend adjusting MMF doses using therapeutic drug monitoring.