Tacrolimus versus Cyclosporine Immunosuppression in Pediatric Renal Transplantation : Pharmacokinetic Consideration

Immunosuppressive therapy in pediatric renal transplant recipients is changing consequence of the increasing number of available immunosuppressive agents. The optimal use of immunosuppressive agents requires a thorough understanding of the pharmacokinetic characteristics, but the information on the pharmacokinetic characteristics of these drugs in pediatric transplant recipients is still limited. In general, patients younger than 5 years old show higher clearance rates, therefore the need for higher dosages in younger patients seems evident. By the therapeutic drug monitoring, trough($C_{min}$) and peak level($C_{max}$) are measured and the area under the blood concentration-time curve(AUC), which is taken as being representative of total systemic exposure can be calculated. Cyclosporine A (CSA) has poor bioavailability, which contributes to high inter- and intra-patient pharmacokinetic variability. CSA concentration measured 2 hours after administration($C_2$) has better correlation with the AUC than $C_{min}$ and is an alternative technique that predicts the AUC. Tacrolimus(Tac) has a great deal of inter-individual variability like CSA but intra-individual variability in systemic exposure is considered to be low. Both CSA and Tac are metabolized by a cytochrome P-450 enzyme isoform(CYP3A4). We should consider changing the dosages when CSA or Tac is used in combination with the medicines that inhibit or induce the CYP3A4. In case of steroid-free immunosuppressive therapy, the blood concentration of Tac should be frequently checked and dosage adjustment may be needed.

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