MODELING OF SUBCUTANEOUS ABSORPTION KINETICS OF INFUSION SOLUTIONS INTHE ELDERLY USING TECHNETIUM

Absorption kinetics of solutes given with the subcutaneous administrat ion of fluids is ill-defined. The gamma emitter, technitium pertechnet ate, enabled estimates of absorption rate to be estimated independentl y using two approaches. In the first approach, the counts remaining at the site were estimated by imaging above the subcutaneous administrat ion site, whereas in the second approach, the plasma technetium concen tration-time profiles were monitored up to 8 hr after technetium admin istration. Boluses of technetium pertechnetate were given both intrave nously and subcutaneously on separate occasions with a multiple dosing regimen using three doses on each occasion. The disposition of techne tium after iv administration was best described by biexponential kinet ics with a V-ss 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 i mage analysis and a half-life of 11.58 +/- 2.48 min using plasma techn etium time data. The bioavailability of technetium by the subcutaneous route was estimated to be 0.96 +/- 0.12. The absorption half-life sho wed no consistent change with the duration of the subcutaneous infusio n. The amount remaining at the absorption site with time was similar w hen analyzed using image analysis, and plasma concentrations assuming multiexponential disposition kinetics and a first-order absorption pro cess. Profiles of fraction remaining at the absorption sire generated by deconvolution analysis, image analysis, and assumption of a constan t first-order absorption process were similar. Slowing of absorption f rom the subcutaneous administration site is apparent after the last bo lus dose in three of the subjects and can De associated with the stopp ing of the infusion. In a fourth subject, the retention of technetium at the subcutaneous site is more consistent with accumulation of techn etium near the absorption site as a result of systemic recirculation.