December 1, 1979Clinical Pharmacology & Therapeutics
Interindividual variation in kinetics of infused epinephrine
Why the study?
What is the interindividual variation in the kinetics of infused norepinephrine in normotensive males?
Population
n=5 normotensive, male laboratory subjects, mean age 32.4 +/- 1.9 years
Design
Other
Follow-up
10 hours
Authors
Discussion
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Implication
Variation in norepinephrine pharmacokinetics limits plasma level comparisons of sympathetic activity; leaves open individualized vasopressor titration in shock.
Key Points
- To assess the pharmacokinetics and hemodynamic responses of sustained norepinephrine infusion and evaluate variability between individuals.
- Infused 1-norepinephrine continuously for 10 hours at a mean rate of 0.06 µg/kg/min into 5 normotensive male laboratory subjects (mean age, 32.4 ± 1.9 years).
- Measured plasma norepinephrine levels, blood pressure, heart rate, metabolic clearance rates, and elimination kinetics across the infusion period.
- Plasma norepinephrine rose from a baseline of 0.19 ± 0.02 µg/L to a steady-state level of 1.22 ± 0.29 µg/L, accompanied by a mean blood pressure rise of 21.8 ± 0.9 mm Hg systolic and 14.1 ± 1.0 mm Hg diastolic, and a heart rate reduction of 12.7 ± 1.7 beats/min.
- Clearance ranged widely between individuals from 27.9 to 100.0 mL/kg/min (mean, 58.0 ± 13.8 mL/kg/min), with a brief elimination half-life ranging from 1.45 to 2.90 minutes (mean, 2.09 ± 0.34 minutes).
Structured PICO
What is the interindividual variation in the kinetics of infused norepinephrine in normotensive males?
P
Population
n=5 normotensive, male laboratory subjects, mean age 32.4 +/- 1.9 years
I
Intervention
1-Norepinephrine infused continuously for 10 hours at a mean rate of 0.06 microgram/kg/min
O
Outcome
Plasma norepinephrine kinetics (clearance, volume of distribution, half-life)surrogate
Wide interindividual variation in norepinephrine kinetics limits the validity of using plasma norepinephrine levels for interindividual comparisons of sympathetic activity.
Cite This Study
FitzGerald et al. (1979) studied this question.