Skip to main content

Advertisement

Log in

Pharmacokinetics of mycophenolate mofetil are influenced by concomitant immunosuppression

Pediatric Nephrology Aims and scope Submit manuscript

Abstract 

The recommended dosage for mycophenolate mofetil (MMF) in combination with cyclosporin (CyA) for pediatric kidney transplant recipients is 600 mg/m2 twice daily (b.i.d.). We recently published pharmacokinetic (PK) profiles of MMF in combination with tacrolimus (FK506): in order to keep the mycophenolic acid (MPA) pre-dose trough concentration between 2 and 5 µg/ml and to avoid side effects, mean MMF doses were reduced to 300 mg/m2 b.i.d.. In order to investigate whether this striking difference was due to alterations of MPA clearance by CyA or FK506, we analyzed PK profiles from 13 patients who received MMF without CyA or FK506, and compared these data with 14 patients who received a combination of MMF and FK506 and 15 patients who received MMF and CyA. Mean area under the curve (AUC) in all PK profiles was 61.9±23.8 µg×h/ml. Although the AUCs did not differ between the groups, the dose per square meter was significantly lower in patients receiving concomitant FK506 compared with CyA, and the dose-normalized AUC was significantly higher. The MMF doses were 1,158±301 mg/m2 per day in the CyA group, 555±289 mg/m2 per day in the tacrolimus group, and 866±401 mg/m2 per day in the group without concomitant calcineurin inhibitor treatment. The apparent clearance of MPA is reduced in combination with tacrolimus. The reason for this remains unknown. There was a trend towards lower dose-normalized AUCs in the CyA group compared with the group without calcineurin inhibitor treatment. We conclude that concomitant medication alters the clearance of MPA. It is noteworthy that there was substantial interindividual variation, despite the rather marked differences between the groups, and therefore we recommend starting MMF in combination with CyA at a dose of 600 mg/m2 b.i.d., in combination with tacrolimus at a dose of 300 mg/m2 b.i.d., and without a calcineurin inhibitor at a dose of 500 mg/m2 b.i.d., and adjusting doses using therapeutic drug monitoring of MPA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Author information

Authors and Affiliations

Authors

Additional information

Received: 2 September 1998 / Revised: 7 January 1999 / Accepted: 7 January 1999

Rights and permissions

Reprints and permissions

About this article

Cite this article

Filler, G., Zimmering, M. & Mai, I. Pharmacokinetics of mycophenolate mofetil are influenced by concomitant immunosuppression. Pediatr Nephrol 14, 100–104 (2000). https://doi.org/10.1007/s004670050021

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s004670050021

Navigation