title: Limited sampling strategies for sirolimus after pediatric renal transplantation.
abstract: SRL has been increasingly used in renal transplantation, but limited sampling approaches for estimation of AUC remain elusive. A post-hoc analysis of 94 PK profiles in 75 patients from four previous studies was performed to generate limited sampling approaches for approximation of AUC based on two to four time points for both BID and OD SRL dosing. AUC was calculated using the trapezoid rule. Stepwise linear regression was performed to generate an abbreviated AUC from the limited sampling approaches. For BID dosing, complete AUC had a strong correlation with the trough levels (r(2) = 0.882, p < 0.0001) and with C2 level (r(2) = 0.9025, p < 0.0001). A three-point and a four-point limited sampling approach showed improved agreement with complete AUC compared with single-point sampling. A convenient and accurate (r(2) = 0.992) four-point limited sampling approach reads: AUC = 10;(1.085 + 0.117 x log C0 + 0.164 x log C1-0.131 x log C2 + 0.823 x log C4). Similarly, complete AUC had a statistically significant correlation with the trough levels (r(2) = 0.549, p < 0.0001) and with C2 level (r(2) = 0.716, p < 0.0001) for OD dosing. The estimation of AUC for OD dosing was improved over single-point sampling (r(2) = 0.951) using the formula: AUC = 10;(1.100 + 0.115 x log C0 + 0.803 x log C4). This study represented the first limited sampling approach for SRL. Further studies are required to determine the optimal SRL target AUC.
authors.affiliation: Department of Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
authors.forename: Nauzer
authors.initials: N
authors.lastname: Forbes
authors.forename: Asher D
authors.initials: AD
authors.lastname: Schachter
authors.forename: Abeer
authors.initials: A
authors.lastname: Yasin
authors.forename: Ajay P
authors.initials: AP
authors.lastname: Sharma
authors.forename: Guido
authors.initials: G
authors.lastname: Filler
mesh_terms: D019540:Area Under Curve; D002648:Child; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D016014:Linear Models; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus