Calculation of plasma concentrations of intra-arterially infused compounds in forearm plethysmography

Forearm blood flow plethysmography is a widely accepted in vivo technique for pharmacologic and functional studies in peripheral resistance vessels and veins. Pharmacological effects on forearm blood flow (FBF) are usually expressed by means of dose-response relationships. This approach does not consider the influence of variations in FBF on the actual plasma concentrations of compounds infused, and is less suitable for quantitative comparison of the pharmacologic characteristics of different compounds. The aim of this study was to validate an equation to estimate the plasma concentrations of intra-arterially infused compounds. This was done at different levels of FBF, using an indicator dilution technique with constant rate infusions of indocyanine green (ICG) and inulin.

ICG (0.5 mg/min) and insulin (5 mg/min) were infused into the brachial artery in the presence of sodium nitroprusside (10 ng/kg/min; to obtain high FBF), vehicle (0.9% saline; for intermediate FBF), and methoxamine (1 microgram/kg/min; for low FBF), FBF was measured using venous occlusion plethysmography in six healthy male volunteers. Plasma concentrations of the indicators, measured in venous blood samples, were compared with the calculated values.

Excellent correspondence was observed between calculated and measured plasma concentrations for both ICG and inulin. Venous plasma concentrations of ICG (> or = 95% protein binding) reached steady-state within four min independent of FBF. Alternatively, the time required for venous plasma concentrations of inulin (not bound to protein) to reach steady-state appeared dependent on FBF.

Total plasma concentrations of intra-arterially infused drugs can be appropriately estimated at the level of the arterioles by the proposed equation.