OBJECTIVES: To develop a method for drug dosing and pharmacokinetic (PK) sampling in children with cancer from a single indwelling central venous catheter that minimized drug contamination. METHODS: A benchtop system was designed to simulate dosing and clearing actinomycin-D (AMD) and vincristine (VCR) from central venous catheters. The authors evaluated the effects of flush volume, composition and pH, timed drug instillation, and number of blood-draw return cycles on residual drug concentrations. A proof-of-principle study was conducted in three pediatric patients with cancer with paired PK samples obtained by both central and peripheral catheters. RESULTS: Nearly complete removal of drug from the catheter was obtained after five blood-draw return cycles consisting of 5 mL of whole blood. Residual concentration of AMD was 0.18 ± 0.02 ng/mL or 0.16% of the initial infusion concentration. VCR exhibited lower propensity for catheter adsorption than AMD with residual concentrations undetectable after three blood-draw return cycles. In patients in which the clearance procedure was used, higher drug concentrations were generally observed from centrally cleared samples at most time points, but differences relative to peripherally obtained samples were not statistically significant for either AMD or VCR. Two of three patients had higher exposure for AMD based on PK samples obtained from central catheters, whereas exposure for VCR was similar for both sampling catheters in all patients. CONCLUSIONS: A reliable procedure to efficiently reduce AMD and VCR contamination during PK sampling has been established and is currently being used in a PK study being conducted by the Children's Oncology Group.
OBJECTIVES: To develop a method for drug dosing and pharmacokinetic (PK) sampling in children with cancer from a single indwelling central venous catheter that minimized drug contamination. METHODS: A benchtop system was designed to simulate dosing and clearing actinomycin-D (AMD) and vincristine (VCR) from central venous catheters. The authors evaluated the effects of flush volume, composition and pH, timed drug instillation, and number of blood-draw return cycles on residual drug concentrations. A proof-of-principle study was conducted in three pediatric patients with cancer with paired PK samples obtained by both central and peripheral catheters. RESULTS: Nearly complete removal of drug from the catheter was obtained after five blood-draw return cycles consisting of 5 mL of whole blood. Residual concentration of AMD was 0.18 ± 0.02 ng/mL or 0.16% of the initial infusion concentration. VCR exhibited lower propensity for catheter adsorption than AMD with residual concentrations undetectable after three blood-draw return cycles. In patients in which the clearance procedure was used, higher drug concentrations were generally observed from centrally cleared samples at most time points, but differences relative to peripherally obtained samples were not statistically significant for either AMD or VCR. Two of three patients had higher exposure for AMD based on PK samples obtained from central catheters, whereas exposure for VCR was similar for both sampling catheters in all patients. CONCLUSIONS: A reliable procedure to efficiently reduce AMD and VCR contamination during PK sampling has been established and is currently being used in a PK study being conducted by the Children's Oncology Group.
Authors: Milly E de Jonge; Ron A A Mathôt; Selma M van Dam; Sjoerd Rodenhuis; Jos H Beijnen Journal: Ther Drug Monit Date: 2003-06 Impact factor: 3.681
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