Niazi S, Chiou W L
J Pharm Sci. 1975 May;64(5):763-9. doi: 10.1002/jps.2600640507.
An intravenous dosage form of trichloromonofluoromethane, a common aerosol propellant, was formulated in polyethylene glycol 400 for single and multiple dosing to unanesthetized dogs. A three-compartment open model was proposed for disposition of this compound in dogs with average half-lives of 3.2, 16, and 93 min for three disposition phases. This finding is contrary to several reports where blood levels were monitored for shorter periods. A computer analysis of tissue compartment distribution following a single dose showed that about 2 hr was required to achieve pseudodistribution equilibration, following which more than 90% of the dose remaining in the body was retained in tissue compartments. Pulmonary clearance and volumes of distribution were calculated considering first-pass effect through the lung. The volume of distribution was approximately six times the body weight in terms of blood concentrations, and about 30% of the propellant was cleared from blood passing through the lung in each cycle. Disposition of propellant followed dose-independent kinetics after multiple dosing, and accumulation in tissues continued for a much longer period, resulting in high tissue compartment levels.
将一种常见的气雾剂推进剂三氯一氟甲烷制成静脉剂型，以聚乙二醇400为溶剂，用于对未麻醉的犬进行单次和多次给药。针对该化合物在犬体内的处置情况，提出了一个三室开放模型，三个处置阶段的平均半衰期分别为3.2分钟、16分钟和93分钟。这一发现与一些监测血药浓度时间较短的报告相反。对单次给药后组织隔室分布的计算机分析表明，达到伪分布平衡大约需要2小时，在此之后，体内剩余剂量的90%以上保留在组织隔室中。考虑到通过肺部的首过效应，计算了肺部清除率和分布容积。就血药浓度而言，分布容积约为体重的6倍，每个循环中约30%的推进剂从流经肺部的血液中清除。多次给药后，推进剂的处置遵循非剂量依赖性动力学，并且在组织中的蓄积持续更长时间，导致组织隔室水平较高。
