Inpharma 1451 - 21 Aug 2004

Mycophenolate mofetil: higherdoses for younger children

"Small children require almost double the dose of[mycophenolate mofetil] when compared withadolescents, even when dosing per body surface area",report investigators from Canada, adding thatpharmacokinetic monitoring of mycophenolate mofetiladministration is necessary due to the large interpatientvariability of the mycophenolic acid AUC.

Their retrospective study involved 27 renal transplantrecipients aged 1.8–20.7 years who were treated withmycophenolate mofetil and tacrolimus for > 3 months;pharmacokinetic monitoring was utilised to ensure atherapeutic mycophenolic acid trough level of 1–5 mg/L.

The mean daily tacrolimus dose was 2.6 mg/m2, witha corresponding average AUC of 120.6 ng – h/mL and aninterpatient coefficient of variation of 67% for drugclearance. A mean daily tacrolimus dose of 3.5 mg/m2

was required to achieve an AUC of 150 ng – h/mL. Themedian daily mycophenolate mofetil dose was549 mg/m2, and the median mycophenolic acid AUCwas 49.8 µg – h/mL, with a 43.5% interpatient coefficientof variation.

All patients were treated with concomitantcorticosteroids, with a mean daily dose of 0.22 mL/kg;the corticosteroid dose was independent of age,however age was a significant independent factor whencorrected for corticosteroid dose. The dosingrequirement for mycophenolate mofetil was increasedfrom 250 mg/m2 in adolescents to 500 mg/m2 twice dailyin children aged 2 years. The investigators note that"underdosing in infants may lead to rejection, whereasoverdosing in adolescents may lead to more toxicity".Filler G, et al. Age-dependency of mycophenolate mofetil dosing in combinationwith tacrolimus after pediatric renal transplantation. Transplantation Proceedings36: 1327-1331, No. 5, Jun 2004 800979164

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Inpharma 21 Aug 2004 No. 14511173-8324/10/1451-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved