DOPAMINE INFUSION IN HEALTHY SUBJECTS AND CRITICALLY ILL PATIENTS

SUMMARY 1. Little is known about the metabolism and the pharmacokinetics of dopamine (DA) in critically ill patients. To study the influence of the total administered DA dose on the disposition of free (i.e. unconjugated) and sulfoconjugated DA, plasma levels of free and sulfoconjugated DA were measured following infusion of 5 μg DA/kg per min for 0.5 and 3 h in six healthy volunteers and in eight critically ill patients receiving DA at the same infusion rate for 6.5 to 329 h. 2. In patients and volunteers steady state concentrations of free DA showing fairly large inter‐individual variations (12.4–73.4 μg/L) were reached within 10 min of the beginning of the infusion. 3. DA sulfate was generated immediately. In volunteers peak values of the sulfoconjugate were observed 15–60 min after the termination of the DA infusion. In patients steady state concentrations of conjugated DA (63–80 μg/L) were reached within 5–10 h of DA infusion. 4. The initial half‐life (t1/2α), the terminal elimination half life (t1/2) and the distribution volume of free DA in the volunteers were significantly higher after 3 h of the DA infusion as compared to the shorter infusion. These parameters as well as the total plasma clearance of free DA were independent of the length of the DA infusion period in patients. The large distribution volumes of 19.8–75 L/kg indicate that DA has been taken up by peripheral tissues. 5. Substantial inter‐individual variations in the patients' clearance of free DA (3.9–16.5 L/kg per h) may partly explain the variability in haemodynamic responses to DA infusion reported in clinical studies. No effects of DA on the systolic and diastolic blood pressures or the plasma concentrations of norepinephrine were found in the healthy subjects. The physiological significance of sulfated DA as a potential reserve pool for free DA has to be further clarified.