To elucidate parameters diagnostic of chronic ischemia, the fluorescence of skin on the foot, leg, arm, and forehead of six chronically ischemic patients and six normal subjects injected with fluorescein was measured serially using a surface‐measurement fluorometer (dermoflu‐orometer). Simultaneously collected plasma samples were assayed spectrofluorometrically for unmetabolized fluorescein. The time courses of plasma fluorescein content and dermofluorometer readings were jointly analyzed by combining a standard pharmacokinetic model, a model predicting skin site from plasma concentrations of fluorescein, and a model predicting the dermofluorometer response to those skin concentrations. Fluorescein plasma clearance (0.22 ± 0.06 versus 0.46 ± 0.20 L/h/kg) in ischemic patients was only half, and half‐life was double (2.4 ± 1.0 versus 1.3 ± 0.3 h) those in normal subjects, with volume of distribution (Vdss = 0.46 L/kg) being similar. Despite the ischemia diagnosis for all patients involving claudication of the lower extremities, patients could be distinguished statistically from normal subjects on the basis of fluorescence readings taken on the arm, but not those using the foot or leg. The rate constant describing flux of fluorescein from the arm skin site in patients was only half that in normal subjects, and the peak reading on the arm occurred at 42 ± 14 min after fluorescein injection in patients, but at only 15 ± 6 min in normal subjects. Lack of discrimination between subject groups via leg and foot readings may be due to several physiologic and/or experimental factors, including the need to take skin surface readings much earlier than previously recognized. As might be expected on optical grounds, the model predicted that the dermofluorometer is less sensitive to similar skin concentrations of fluorescein in people of black as compared with white ethnic background.
ASJC Scopus subject areas
- Pharmaceutical Science