Roberts M S, Lipschitz S, Campbell A J, Wanwimolruk S, McQueen E G, McQueen M
Department of Medicine, University of Queensland, Princess Alexandra Hospital, Australia.
J Pharmacokinet Biopharm. 1997 Feb;25(1):1-21. doi: 10.1023/a:1025763509326.
Absorption kinetics of solutes given with the subcutaneous administration of fluids is ill-defined. The gamma emitter, technitium pertechnetate, enabled estimates of absorption rate to be estimated independently using two approaches. In the first approach, the counts remaining at the site were estimated by imaging above the subcutaneous administration site, whereas in the second approach, the plasma technetium concentration-time profiles were monitored up to 8 hr after technetium administration. Boluses of technetium pertechnetate were given both intravenously and subcutaneously on separate occasions with a multiple dosing regimen using three doses on each occasion. The disposition of technetium after i.v. administration was best described by biexponential kinetics with a Vss of 0.30 +/- 0.11 L/kg and a clearance of 30.0 +/- 13.1 ml/min. The subcutaneous absorption kinetics was best described as a single exponential process with a half-life of 18.16 +/- 3.97 min by image analysis and a half-life of 11.58 +/- 2.48 min using plasma technetium time data. The bioavailability of technetium by the subcutaneous route was estimated to be 0.96 +/- 0.12. The absorption half-life showed no consistent change with the duration of the subcutaneous infusion. The amount remaining at the absorption site with time was similar when analyzed using image analysis, and plasma concentrations assuming multiexponential disposition kinetics and a first-order absorption process. Profiles of fraction remaining at the absorption site generated by deconvolution analysis, image analysis, and assumption of a constant first-order absorption process were similar. Slowing of absorption from the subcutaneous administration site is apparent after the last bolus dose in three of the subjects and can be associated with the stopping of the infusion. In a fourth subject, the retention of technetium at the subcutaneous site is more consistent with accumulation of technetium near the absorption site as a result of systemic recirculation.
皮下注射液体时溶质的吸收动力学尚不明确。γ发射体高锝酸盐能够通过两种方法独立估算吸收速率。在第一种方法中,通过对皮下给药部位上方进行成像来估算该部位剩余的计数,而在第二种方法中,在给予锝后长达8小时监测血浆锝浓度-时间曲线。在不同时间分别静脉内和皮下给予高锝酸盐推注,采用多剂量方案,每次给予三剂。静脉内给药后锝的处置情况用双指数动力学能得到最佳描述,稳态分布容积为0.30±0.11L/kg,清除率为30.0±13.1ml/min。皮下吸收动力学通过图像分析用单指数过程能得到最佳描述,半衰期为18.16±3.97分钟,而使用血浆锝时间数据时半衰期为11.58±2.48分钟。皮下途径的锝生物利用度估计为0.96±0.12。吸收半衰期随皮下输注持续时间无一致变化。使用图像分析以及假设多指数处置动力学和一级吸收过程分析血浆浓度时发现,吸收部位随时间剩余的量相似。通过反卷积分析、图像分析以及假设恒定一级吸收过程生成的吸收部位剩余分数曲线相似。在三名受试者中,最后一次推注剂量后皮下给药部位的吸收明显减慢,这可能与输注停止有关。在第四名受试者中,皮下部位锝的滞留更符合由于全身再循环导致锝在吸收部位附近蓄积的情况。