Everolimus in pediatric de nova renal transplant patients1
Everolimus in pediatric de nova renal transplant patients1
复制标题
依维莫司在儿童新肾移植患者中的应用1
DOI：
10.1097/01.tp.0000070139.63068.54
复制
发表时间：
2003
期刊：
影响因子：
6.2
通讯作者：
H. Mayer
中科院分区：
文献类型：
--
作者：
P. Hoyer;R. Ettenger;J. Kovarik;N. Webb;J. Lemire;M. Mentser;J. Mahan;C. Loirat;P. Niaudet;R. Vandamme;G. Offner;S. Wehr;V. Moeller;H. Mayer
Background. The steady-state pharmacokinetics of everolimus were longitudinally assessed in pediatric de novo kidney allograft recipients during a 6-month period. Methods. Nineteen patients received everolimus 0.8 mg/m2 (maximum 1.5 mg) twice daily as a dispersible tablet in water in addition to cyclosporine and corticosteroids. Everolimus and cyclosporine trough concentrations were obtained on days 3, 5, 6, and 7 and at months 1, 2, 3, and 6; an everolimus pharmacokinetic profile was obtained on day 7 and month 3. Results. There were 9 boys and 10 girls with a median age of 9.9 (range, 1–16) years. Steady-state pharmacokinetic parameters were as follows (median, range): Cmin (trough level), 4.7 (2.3- 9.5) ng/mL; peak concentration, 13.5 (5.9–22.2) ng/mL; area under the concentration-time curve (AUC), 77 (53–147) ng·hr/mL; and apparent oral clearance, 10.2 (5.5–15.6) L/hr/m2. Clearance (unadjusted for demographic factors) was positively correlated with age (r =0.66), body surface area (r =0.68), and weight (r =0.67). There were no trends in Cmin or AUC versus patient age when everolimus was dosed on a mg/m2 basis. Everolimus Cmin were stable over time with median values of 3.9, 3.4, and 3.1 ng/mL at months 1, 3, and 6, respectively. Intra- and interpatient variability in AUC was 29% and 35%, similar to that in adults. During the observation period, eight patients maintained stable AUCs and nine patients had increases or decreases, generally between 30% and 50% compared with the AUC at week 1. The concurrent median cyclosporine Cmin were generally at the lower end of conventional target ranges: 156, 83, and 69 ng/mL at months 1, 3, and 6, respectively. There were no graft losses and only three mild or moderate, reversible rejection episodes occurred. Everolimus was generally safe and well tolerated. Conclusions. These data support the use of body surface area-adjusted dosing for everolimus in pediatric patients. Although exposure is generally stable over time with moderate variability in AUC, therapeutic monitoring would be a helpful adjunct for individualizing everolimus exposure, assessing regimen adherence, and adjusting doses as the child matures.
影响因子：
19.6
作者：
SOLEZ, K;AXELSEN, RA;YAMAGUCHI, Y
通讯作者：
YAMAGUCHI, Y