Mason N A, Cline S, Hyneck M L, Berardi R R, Ho N F, Flynn G L
Am J Hosp Pharm. 1981 Oct;38(10):1449-54.
The sorption of diazepam in large-volume i.v. admixtures to administration-set components and in i.v. containers was analyzed quantitatively. Solubility of diazepam in phosphate buffer at various pH levels and in i.v. fluids was measured. Partition coefficients of diazepam into components of i.v. administration sets and i.v. containers were studied by shaking a solution of diazepam in 0.9% sodium chloride, with finely cut components and measuring the change in diazepam in the aqueous phase. Flow studies through an administration set of a 0.04-mg/ml diazepam solution in 5% dextrose injection were done, varying both the flow rate and the length of tubing. The maximum free-base solubility of diazepam in phosphate buffer was 0.048 mg/ml; its solubility was 0.058, 0.050, and 0.064 mg/ml in lactated Ringer's, 0.9% sodium chloride, and 5% dextrose injections, respectively. Equilibrium partition coefficients were highest for polyvinyl chloride tubing and flexible bags. Volume-control sets made of cellulose propionate had lower but sufficiently large partition coefficients to cause diazepam loss. Polyolefin semi-rigid and glass containers had low partition coefficients. In the flow studies, the amount of solution-contact time correlated with the extent of absorption. As flow rate decreased or tubing length increased, the amount of diazepam absorbed increased proportionately. A nomogram and a predictive dosing chart are presented for calculation of actual diazepam doses delivered at various flow rates and tubing lengths. Diazepam can be administered safely and effectively by i.v. infusion. The use of volume-control sets and flexible polyvinyl chloride bags should be avoided with diazepam solutions. Polyolefin semi-rigid containers are acceptable alternatives to glass. The concentration of diazepam infusions should not exceed 0.04 mg/ml.
分析了地西泮在大容量静脉内混合液中对给药装置组件和静脉内容器的吸附情况，并进行了定量分析。测定了地西泮在不同pH值的磷酸盐缓冲液和静脉内液体中的溶解度。通过将地西泮在0.9%氯化钠溶液中的溶液与精细切割的组件振荡，并测量水相中地西泮的变化，研究了地西泮在静脉内给药装置组件和静脉内容器中的分配系数。对5%葡萄糖注射液中0.04mg/ml地西泮溶液通过给药装置进行了流量研究，改变了流速和管路长度。地西泮在磷酸盐缓冲液中的最大游离碱溶解度为0.048mg/ml；其在乳酸林格氏液、0.9%氯化钠注射液和5%葡萄糖注射液中的溶解度分别为0.058mg/ml、0.050mg/ml和0.064mg/ml。聚氯乙烯管路和软袋的平衡分配系数最高。由丙酸纤维素制成的容量控制装置的分配系数较低，但足以导致地西泮损失。聚烯烃半刚性容器和玻璃容器的分配系数较低。在流量研究中，溶液接触时间与吸收程度相关。随着流速降低或管路长度增加，地西泮的吸收量成比例增加。给出了一个列线图和一个预测给药图表，用于计算在不同流速和管路长度下实际输送的地西泮剂量。地西泮可通过静脉输注安全有效地给药。地西泮溶液应避免使用容量控制装置和软质聚氯乙烯袋。聚烯烃半刚性容器是玻璃的可接受替代品进行。地西泮输注的浓度不应超过0.04mg/ml。
