| Abstrakt: |
Kim JS, Aviles DH, Silverstein DM, LeBlanc PL, Vehaskari VM. Effect of age, ethnicity, and glucocorticoid use on tacrolimus pharmacokinetics in pediatric renal transplant patients.Pediatr Transplantation 2005.© 2005 Blackwell MunksgaardTacrolimus has become an effective alternative to cyclosporine as a component of primary immunosuppression in pediatric renal transplant patients, but the information on the pharmacokinetic characteristics of tacrolimus in young patients is still limited. The primary objective of this study was to determine the effect of patient age, ethnicity, and concurrent steroid administration on tacrolimus pharmacokinetics in pediatric renal transplant patients. The study population consisted of 30 pediatric patients, age 1.5–18.6 yr, who received a kidney transplant between July 1999 and February 2004. After twice daily dosing was stabilized based on clinical judgment, at least 5 days postoperatively, tacrolimus levels were drawn prior to, and 1, 2, 4, 8, and 12 h after the morning dose. The mean dose of tacrolimus was 0.12 mg/kg/dose. Mean trough level was 11.9 ± 5.0 ng/mL. Mean area under the curve (AUC) was 192 ± 84 with a range of 78–360 h × (ng/mL). The correlation between trough level andAUCwas only fair (r = 0.74); later time points correlated better withAUC, and an excellent correlation (r = 0.96) was obtained between the mean of trough and 2-h level (C2) andAUC. There was a negative correlation between age and dose per body weight (r = −0.68). African-American patients had marginally lower drug exposure with similar dosing. Three age groups (<5, 5–12, and>12 yr) were compared with respect to dosing andAUC. Despite similarAUCin all three groups, the mean dose per kg required to achieve theAUCwas 2.7- and 1.9-fold higher in the<5 and 5–12-yr groups, respectively, compared with the>12-yr group. Nine of the 30 patients were on a totally steroid-free regimen. Their tacrolimus dose and trough levels were similar to those of steroid-exposed patients, but their meanAUCwas 41% higher. Our results show an inverse correlation between age and required tacrolimus dose, wide interindividual variation, and greater exposure with steroid-free regimen despite no change in trough level. [ABSTRACT FROM AUTHOR] |
