Blood flow measurements in skin and underlying tissues by microsphere method: application to dermal pharmacokinetics of polar nonelectrolytes.

Blood flow rates to skin and underlying tissues in rats were determined by the radioactive microsphere technique. The dermal and local tissue clearance of two polar solutes, tritiated water and 14C-labeled sucrose, was assessed in anesthetized and sacrificed rats. The dermal clearance of tritiated water in the presence of viable dermal blood supply (6.17 +/- 1.41 mL/min/100 g) was similar in magnitude but more variable than the blood flow to skin estimated by the microsphere technique (5.18 +/- 0.25 mL/min/100 g). The dermal clearance of sucrose (1.66 +/- 0.32 mL/min/100 g) was approximately one quarter the dermal clearance for water, the difference corresponding to the free diffusion coefficients of the two solutes. The permeability coefficients of tritiated water in various tissues were estimated by both a pseudo-steady-state mass balance approach and numerical integration of differential equations (for dermis only) with a "series compartmental" model, from the tissue concentrations obtained in sacrificed rats. The estimates from numerical integration were comparable to those obtained by mass balance, confirming the general structure of the model. The observed tissue concentrations of tritiated water and sucrose in the anesthetized animal compared well with values predicted from the model.