Correlation between the pharmacokinetics and pharmacodynamics of dopamine in healthy subjects

Abstract

The pharmacokinetics and the pharmacodynamic action of dopamine were investigated in 5 healthy subjects. Dopamine was given in different doses (200, 400 and 800 µg/min) by constant intravenous infusion over 90 min. In order to control the influence of the procedure on the measured parameters the subjects also received a similar infusion of saline. Dopamine, noradrenaline and adrenaline levels in plasma were followed for up to 6 h after the infusion, and arterial pressure and heart rate were monitored. Dopamine reached a steady state level within 15 to 30 min after commencement of the infusion; the steady state levels averaged 36.5 µg/l at 200 µg/min, 73.8 µg/l at 400 µg/min and 207 µg/l at 800 µg/min. The corresponding total clearances were 5.8 l/ min, 5.51/min and 3.9 l/min suggesting non-linear kinetics. The kinetics could not be described by compartmental model. Noradrenaline and adrenaline levels were found to be elevated during infusion of dopamine. Noradrenaline had returned to its pretreatment level within 15 to 30 min after cessation of the infusion, whereas the adrenaline level did not return to the pretreatment value within the observation period. Heart rate was increased by the dose of 400 µg/min, and the systolic and mean arterial pressures were elevated, whereas distolic blood pressure remained unchanged. Elevated systolic blood pressure was better correlated with plasma dopamine than with noradrenaline concentration. This finding, in conjunction with the unchanged diastolic blood pressure, indicates that elevation of the systolic blood pressure is a direct rather than an indirect effect of dopamine. The increased heart rate was not correlated with the dopamine level.