Everolimus in pediatric de nova renal transplant patients.
Transplantation
; 75(12): 2082-5, 2003 Jun 27.
Article
em En
| MEDLINE
| ID: mdl-12829916
ABSTRACT
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) C(min) (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 x 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 C(min) or AUC versus patient age when everolimus was dosed on a mg/m2 basis. Everolimus C(min) 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 C(min) 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante de Rim
/
Sirolimo
/
Imunossupressores
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
Limite:
Adolescent
/
Child
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Child, preschool
/
Female
/
Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article