TY - JOUR
T1 - Development and validation of limited sampling models for topotecan lactone pharmacokinetic studies in children
AU - Turner, P. Kellie
AU - Iacono, Lisa C.
AU - Panetta, John C.
AU - Santana, Victor M.
AU - Daw, Najat C.
AU - Gajjar, Amar
AU - Stewart, Clinton F.
N1 - Funding Information:
Supported in part by US Public Health Service award CA23099 and the American Lebanese Syrian Associated Charities (ALSAC).
PY - 2006/4
Y1 - 2006/4
N2 - Purpose: To develop and validate a pharmacokinetic limited sampling model (LSM) for intravenous and oral topotecan pharmacokinetic studies in children. Methods: Topotecan lactone concentration-time data from five trials were used to develop and validate LSM for intravenous and oral topotecan. Based on full sampling from one intravenous study (30 patients; 195 studies), a LSM for intravenous topotecan was determined using a modification of the D-optimality algorithm. For oral topotecan we used full sampling data from one oral topotecan study (27 patients; 47 studies) to develop an LSM. Accuracy and bias of each LSM were determined relative to the full sampling method. Predictive performance of the LSM was validated using additional data and Monte-Carlo simulations based on these data. Results: LSM for intravenous topotecan includes: 5 min, 1.5, and 2.5 h after the end of the 30 min infusion. The median accuracy (absolute predicted error) and bias (predicted error) are ≤ 8% and ≤ 6.1%, respectively. For oral topotecan, the optimal LSM includes: 15 min, 1.5, and 6 h. The median accuracy and bias are 6% and 4%, respectively. Conclusions: Our results indicate that the optimal sampling times for the intravenous LSM for topotecan in children consist of: predose, and 5 min, 1.5, and 2.5 h after the end of infusion. For oral topotecan the sample times are predose, 15 min, 1.5, and 6 h after dose administration. These LSM are invaluable to children receiving topotecan because it minimizes inconvenience and blood collection.
AB - Purpose: To develop and validate a pharmacokinetic limited sampling model (LSM) for intravenous and oral topotecan pharmacokinetic studies in children. Methods: Topotecan lactone concentration-time data from five trials were used to develop and validate LSM for intravenous and oral topotecan. Based on full sampling from one intravenous study (30 patients; 195 studies), a LSM for intravenous topotecan was determined using a modification of the D-optimality algorithm. For oral topotecan we used full sampling data from one oral topotecan study (27 patients; 47 studies) to develop an LSM. Accuracy and bias of each LSM were determined relative to the full sampling method. Predictive performance of the LSM was validated using additional data and Monte-Carlo simulations based on these data. Results: LSM for intravenous topotecan includes: 5 min, 1.5, and 2.5 h after the end of the 30 min infusion. The median accuracy (absolute predicted error) and bias (predicted error) are ≤ 8% and ≤ 6.1%, respectively. For oral topotecan, the optimal LSM includes: 15 min, 1.5, and 6 h. The median accuracy and bias are 6% and 4%, respectively. Conclusions: Our results indicate that the optimal sampling times for the intravenous LSM for topotecan in children consist of: predose, and 5 min, 1.5, and 2.5 h after the end of infusion. For oral topotecan the sample times are predose, 15 min, 1.5, and 6 h after dose administration. These LSM are invaluable to children receiving topotecan because it minimizes inconvenience and blood collection.
KW - Limited sampling model
KW - Pharmacokinetics
KW - Topotecan
UR - http://www.scopus.com/inward/record.url?scp=30644471976&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=30644471976&partnerID=8YFLogxK
U2 - 10.1007/s00280-005-0062-z
DO - 10.1007/s00280-005-0062-z
M3 - Article
C2 - 16047146
AN - SCOPUS:30644471976
SN - 0344-5704
VL - 57
SP - 475
EP - 482
JO - Cancer chemotherapy and pharmacology
JF - Cancer chemotherapy and pharmacology
IS - 4
ER -