Steady-state pharmacokinetics of dopamine in adult patients

Abstract

To study the pharmacokinetics of dopamine in hemodynamically stable adult patients. Prospective clinical study. University hospital intensive care unit. Fourteen patients (aged 43 to 73 yrs) recovering from esophageal surgery. Dopamine was infused and blood samples were collected. Plasma dopamine concentrations were measured at steady state and subsequently at the end of the dopamine infusion using high-performance liquid chromatography. Clearances, volume of distribution, mean residence times, half-lives, and elimination and distribution rate constants were derived. The clearances were independent of the infusion rate at 1, 3, and 6 micrograms/kg/min, and ranged between 0.050 and 0.056 L/min/kg. A two-compartment open model was fitted to the postinfusion plasma concentration data obtained at 3 and 6 micrograms/kg/min. On average, the steady-state volume of distribution and the apparent terminal elimination half-life increased with the dose: 0.78 to 1.58 L/kg, respectively, and 22.1 to 37.9 mins, respectively, for the rates of 3 and 6 micrograms/kg/min. The rate constant associated with the uptake of dopamine into the peripheral compartment (K12) was on average four to five times higher than the rate constant associated with the reverse process (K21). The redistribution of dopamine into the central compartment could be the main factor involved in the apparent terminal elimination of dopamine from plasma. Due to the relative rates of distribution and elimination, the attainment of a steady-state plasma concentration of dopamine should only depend on the terminal half-life. These results, which remain to be validated in a greater number of patients, indicate that the attainment of 90% of the plateau (i.e., in 3.3 half-lives) would require 70 to 125 mins, depending on the infusion rate.