In vitro approach to study the influence of the cardiac output distribution on drug concentration

Summary

Blood flow is not constant during the day, not only due to cardiac output variation but to the variable blood flow fraction supplied to the organs. To what extent these variations could affect the relative drug concentration between two different tissues, is the purpose of this work. In order to study that, a device was designed which took into account different fluid flows towards two flasks. Connections between flasks and pump are shown in text (figure 1). At the bottom of each flask a non-miscible liquid (dichloromethane: CH₂Cl₂, 100 mL, places 2 and 3) with the circulating fluid (water, 1350 mL, places 1, A, B) was placed. Malachite Green (MG) was introduced as solute into the system (place 1,5 mL, 700 mg/L aqueous solution). The pump output was set at 1080 mL/min, serving more fluid (five times) to flask A than to flask B. Samples were drawn from compartments 1, A and B, and from organic compartments, during experiences taking several hours. MG concentrations were colorimetrically measured at 619 nm. Room temperature was between 15–25 °C. CH₂Cl₂ MG concentration ratio ([2]/[3]) was similar to fluid flow ratio (σ/(1-σ)) all over the experience time. Other experiences changing the stop time, room temperature, CH₂Cl₂ volumes and places, pump output distribution, led us to different evidences that supported a theoretical model. As a conclusion, the most important feature was that whereas MG concentrations in water (1, A, B) were close, in CH₂Cl₂ these were very different. So, is drug effect prediction reliable by monitoring free drug concentrations in blood?