dopamine Hydrochloride in 5% dextrose injection, USP Clinical Pharmacology

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12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Dopamine is a natural catecholamine formed by the decarboxylation of 3,4-dihydroxyphenylalanine (DOPA). It is a precursor to norepinephrine in noradrenergic nerves and is also a neurotransmitter in certain areas of the central nervous system, especially in the nigrostriatal tract, and in a few peripheral sympathetic nerves.

Dopamine elicits its pharmacological action by activating dopamine D1 and D2 receptors, beta-1 receptors and alpha-1 receptors. The activation of different receptors leading to its effects are dependent on dopamine dose.

12.2 Pharmacodynamics

Dopamine's onset of action occurs within five minutes of intravenous administration and the duration of action is less than about ten minutes. Dopamine effects are dosage-dependent.

  • At <5 mcg/kg/minute, dopamine HCl activates dopamine D1 and D2 receptors in the renal, mesenteric, and coronary vasculature causing vasodilation.
  • At 5 to 10 mcg/kg/minute, dopamine HCl activates beta-1 receptors enhancing heart rate and contractility.
  • At >10 mcg/kg/minute, dopamine HCl activates alpha-1 receptors causing vasoconstriction and increased blood pressure

12.3 Pharmacokinetics

Distribution

Following intravenous administration, dopamine is widely distributed in the body but does not cross the blood-brain barrier to a significant extent.

Elimination

The half-life of dopamine in adults is less than 2 minutes.

Metabolism

About 75% of dopamine is metabolized by monoamine oxidase (MAO) and catechol O-methyl transferase (COMT) in the liver, kidney, and plasma to the inactive compounds homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid, and about 25% is metabolized to norepinephrine in the adrenergic nerve terminals.

Excretion

About 80% of dopamine is renally excreted as inactive metabolites within 24 hours. Dopamine is stored in vesicles or diffused back into the plasma.

Specific Populations

Pediatric Patients

The reported clearance rate of dopamine in critically ill infants and pediatric patients ranged from 46 to 168 mL/kg/minute, with the higher values seen in the younger patients. The reported apparent volume of distribution in neonates was 0.6 to 4 L/kg, leading to an elimination half-life of 5 to 11 minutes.

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Clinical Pharmacology

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Dopamine is a natural catecholamine formed by the decarboxylation of 3,4-dihydroxyphenylalanine (DOPA). It is a precursor to norepinephrine in noradrenergic nerves and is also a neurotransmitter in certain areas of the central nervous system, especially in the nigrostriatal tract, and in a few peripheral sympathetic nerves.

Dopamine elicits its pharmacological action by activating dopamine D1 and D2 receptors, beta-1 receptors and alpha-1 receptors. The activation of different receptors leading to its effects are dependent on dopamine dose.

12.2 Pharmacodynamics

Dopamine's onset of action occurs within five minutes of intravenous administration and the duration of action is less than about ten minutes. Dopamine effects are dosage-dependent.

  • At <5 mcg/kg/minute, dopamine HCl activates dopamine D1 and D2 receptors in the renal, mesenteric, and coronary vasculature causing vasodilation.
  • At 5 to 10 mcg/kg/minute, dopamine HCl activates beta-1 receptors enhancing heart rate and contractility.
  • At >10 mcg/kg/minute, dopamine HCl activates alpha-1 receptors causing vasoconstriction and increased blood pressure

12.3 Pharmacokinetics

Distribution

Following intravenous administration, dopamine is widely distributed in the body but does not cross the blood-brain barrier to a significant extent.

Elimination

The half-life of dopamine in adults is less than 2 minutes.

Metabolism

About 75% of dopamine is metabolized by monoamine oxidase (MAO) and catechol O-methyl transferase (COMT) in the liver, kidney, and plasma to the inactive compounds homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid, and about 25% is metabolized to norepinephrine in the adrenergic nerve terminals.

Excretion

About 80% of dopamine is renally excreted as inactive metabolites within 24 hours. Dopamine is stored in vesicles or diffused back into the plasma.

Specific Populations

Pediatric Patients

The reported clearance rate of dopamine in critically ill infants and pediatric patients ranged from 46 to 168 mL/kg/minute, with the higher values seen in the younger patients. The reported apparent volume of distribution in neonates was 0.6 to 4 L/kg, leading to an elimination half-life of 5 to 11 minutes.

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