PDF(Pubmed)
Abstract：
OBJECTIVE: 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.
CONCLUSIONS: The pharmacokinetic profile for doxorubicin in the investigated tissues is very similar when comparing bolus and 6 h continuous infusion.
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.
CONCLUSIONS: The pharmacokinetic profile for doxorubicin in the investigated tissues is very similar when comparing bolus and 6 h continuous infusion.
摘要：
目的：阿霉素是一种广泛使用的化疗药物，可以通过推注和连续输注进行静脉给药。后者被认为可以降低心脏毒性的风险，这是阿霉素治疗的严重长期并发症。阿霉素的局部组织浓度将反映在治疗功效和毒性中，但是可以获得的信息非常有限。这项研究的目的是在骨肿瘤典型位置周围的组织区室中连续推注和推注后，测量阿霉素的浓度。
方法：16头猪（雌性，丹麦长白鱼,平均体重77kg）随机分为两组，每组8个。两组均接受静脉输注150mg阿霉素；第1组接受推注输注（10-15分钟），第2组接受连续输注（6小时）。输液前,静脉内放置微透析导管，并放置在四个骨肿瘤相关的组织区室中（松质骨，皮下组织,膝关节和肌肉组织的滑液）。在24小时内进行采样（n=15），收集静脉血样本作为参考。
结果：血浆（总浓度）的浓度-时间曲线下面积（AUC0-24h）在两组之间存在显着差异，而与第2组相比，第1组的两个隔室（膝关节的血浆和滑液）中的峰值药物浓度（Cmax）明显更高。总的来说,未结合组织浓度极低,低于0.20µg/mL.
结论：当比较推注和6小时连续输注时，所研究组织中阿霉素的药代动力学曲线非常相似。
方法：16头猪（雌性，丹麦长白鱼,平均体重77kg）随机分为两组，每组8个。两组均接受静脉输注150mg阿霉素；第1组接受推注输注（10-15分钟），第2组接受连续输注（6小时）。输液前,静脉内放置微透析导管，并放置在四个骨肿瘤相关的组织区室中（松质骨，皮下组织,膝关节和肌肉组织的滑液）。在24小时内进行采样（n=15），收集静脉血样本作为参考。
结果：血浆（总浓度）的浓度-时间曲线下面积（AUC0-24h）在两组之间存在显着差异，而与第2组相比，第1组的两个隔室（膝关节的血浆和滑液）中的峰值药物浓度（Cmax）明显更高。总的来说,未结合组织浓度极低,低于0.20µg/mL.
结论：当比较推注和6小时连续输注时，所研究组织中阿霉素的药代动力学曲线非常相似。
