PI-052 - CYCLOPHOSPHAMIDE POPULATION PHARMACOKINETICS IN PEDIATRIC PATIENTS UNDERGOING HEMATOPOIETIC STEM CELL TRANSPLANTATION.

J. Brooks¹, B. Solans¹, K. Howard¹, C. Dvorak¹, N. Lalefar², E. Anderson³, Y. Lu¹, R. Savic¹, J. Long-Boyle¹; ¹University of California, San Francisco, San Francisco, CA, USA, ²UCSF Benioff Children's Hospital - Oakland, Oakland, CA, USA, ³Rady Children's Hospital San Diego, San Diego, CA, USA.

Background: Cyclophosphamide (CY) is a DNA alkylating agent commonly used in pediatric hematopoietic stem cell transplantation (HCT) as a part of combination pre-transplant conditioning. Recent PK/PD work in pediatric HCT has led to improvement in dosing strategies for other chemotherapeutic agents used in HCT; however, data on the PK of CY in pediatrics as well as its relationship to clinical efficacy and toxicity in HCT remains limited.

Methods: This is a prospective, multicenter PK study including the three pediatric HCT centers within the US. All patients enrolled in this analysis received CY intravenously and time concentration data were available from 12 participants, including a total of 25 CY and 15 CY-OH samples, respectively. Data analysis and PopPK modeling were completed NONMEM, PsN, and R.

Results: A one-compartment model with between-subject variability on clearance (CL) and volume of distribution (V) best fit the data. Inclusion of patient-specific covariates was not supported by the data. An additive error model was used. Incorporating of CY-OH into the model resulted in model instability and was, therefore, not included in the final model. CY CL and V were estimated at 3.75 L/h (11% RSE) and 14.2 L (11.5% RSE), respectively. Interindividual variability on CL and V are estimated at 2.2% CV and 6.7% CV.

Conclusion: A one-compartmental model without patient-specific covariates well captured the available cyclophosphamide PK data in this study and generated parameter estimates in line with published values. Enrollment is ongoing to increase the sample size which will enable a more robust analysis with the long-term goal of improved dosing strategies in children undergoing HCT.