TY - JOUR
T1 - Doxorubicin concentrations in bone tumour-relevant tissues after bolus and continuous infusion
T2 - a randomized porcine microdialysis study
AU - Jørgensen, Andrea René
AU - Bue, Mats
AU - Hanberg, Pelle
AU - Petersen, Elisabeth Krogsgaard
AU - Harlev, Christina
AU - Hansen, Jakob
AU - Baad-Hansen, Thomas
AU - Safwat, Akmal
AU - Stilling, Maiken
PY - 2024/6
Y1 - 2024/6
N2 - Purpose: Doxorubicin is a widely used chemotherapeutic drug that can be administered intravenously as both a bolus infusion and a continuous infusion. The latter is believed to lower the risk of cardiotoxicity, which is a critical long-term complication of doxorubicin treatment. The local tissue concentrations of doxorubicin will be reflected in both treatment efficacy and toxicity, but very limited information is available. The aim of this study was to measure the concentration of doxorubicin after continuous and bolus infusion in tissue compartments around a typical location of a bone tumour. Methods: Sixteen pigs (female, Danish Landrace, mean weight 77 kg) were randomized into two groups of eight. Both groups received an intravenous infusion of 150 mg doxorubicin; Group 1 received a bolus infusion (10–15 min) and Group 2 received a continuous infusion (6 h). Before infusion, microdialysis catheters were placed intravenously and in four bone tumour-relevant tissue compartments (cancellous bone, subcutaneous tissue, synovial fluid of the knee joint and muscle tissue). Sampling was done (n = 15) over 24 h, and venous blood samples were collected as a reference. Results: Area under the concentration–time curve (AUC0–24 h) for plasma (total concentration) was significantly different between the two groups, while peak drug concentration (Cmax) was significantly higher in two compartments (plasma and synovial fluid of the knee joint) in Group 1 compared to Group 2. Overall, the unbound tissue concentrations were extremely low with values below 0.20 µg/mL. Conclusion: The pharmacokinetic profile for doxorubicin in the investigated tissues is very similar when comparing bolus and 6 h continuous infusion.
AB - Purpose: Doxorubicin is a widely used chemotherapeutic drug that can be administered intravenously as both a bolus infusion and a continuous infusion. The latter is believed to lower the risk of cardiotoxicity, which is a critical long-term complication of doxorubicin treatment. The local tissue concentrations of doxorubicin will be reflected in both treatment efficacy and toxicity, but very limited information is available. The aim of this study was to measure the concentration of doxorubicin after continuous and bolus infusion in tissue compartments around a typical location of a bone tumour. Methods: Sixteen pigs (female, Danish Landrace, mean weight 77 kg) were randomized into two groups of eight. Both groups received an intravenous infusion of 150 mg doxorubicin; Group 1 received a bolus infusion (10–15 min) and Group 2 received a continuous infusion (6 h). Before infusion, microdialysis catheters were placed intravenously and in four bone tumour-relevant tissue compartments (cancellous bone, subcutaneous tissue, synovial fluid of the knee joint and muscle tissue). Sampling was done (n = 15) over 24 h, and venous blood samples were collected as a reference. Results: Area under the concentration–time curve (AUC0–24 h) for plasma (total concentration) was significantly different between the two groups, while peak drug concentration (Cmax) was significantly higher in two compartments (plasma and synovial fluid of the knee joint) in Group 1 compared to Group 2. Overall, the unbound tissue concentrations were extremely low with values below 0.20 µg/mL. Conclusion: The pharmacokinetic profile for doxorubicin in the investigated tissues is very similar when comparing bolus and 6 h continuous infusion.
KW - Bone Cancer
KW - Doxorubicin
KW - Doxorubicinol
KW - Infusion
KW - Microdialysis
UR - http://www.scopus.com/inward/record.url?scp=85184414330&partnerID=8YFLogxK
U2 - 10.1007/s00280-023-04637-1
DO - 10.1007/s00280-023-04637-1
M3 - Journal article
C2 - 38332155
AN - SCOPUS:85184414330
SN - 0344-5704
VL - 93
SP - 555
EP - 564
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
IS - 6
ER -