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Plasma concentration and acute clinical effects of docarpamine, orally active dopamine prodrug, in infants
1Department of Pediatrics, School of Medicine, Sapporo Medical University, Hokkaido, Japan.
Insights
This study explored docarpamine
Area of Science:
- Pediatric Cardiology
- Pharmacology
- Neonatal Research
Background:
- Limited data exists on docarpamine's optimal dosage and efficacy in infants.
- Docarpamine is a potential therapeutic agent for heart conditions in neonates.
Purpose of the Study:
- To determine the optimal doses and efficacy of oral docarpamine in infants with heart failure.
- To assess the pharmacokinetic and hemodynamic effects of docarpamine in this population.
Main Methods:
- Ten infants with heart failure received oral docarpamine at doses of 15.0-20.4 mg/kg every 8 hours.
- Plasma free dopamine concentrations, heart rate, and blood pressure were monitored.
- Urinary output and electrolyte excretion were measured in a subset of infants.
Main Results:
- Peak plasma concentrations of free dopamine were achieved 1-2 hours post-administration.
- A trend towards increased heart rate and systolic blood pressure was observed.
- No significant changes in urinary output or electrolyte excretion were noted.
Conclusions:
- Oral docarpamine at 15-20 mg/kg per dose can achieve therapeutic plasma dopamine levels in infants.
- The drug demonstrated a potential to increase heart rate and systolic blood pressure, warranting further investigation.
Abstract:
Currently, there are no data available on the optimal doses and efficacy of docarpamine in infants. In the present study, three doses of docarpamine, 15.0-20.4 (19.0 +/- 1.9; mean +/- SD) mg/kg per dose every 8 h to 10 infants suffering heart failure. Age and bodyweight were from 1 to 4 (1.4 +/- 1) months and 2960-5160 (3350 +/- 872) g, respectively. In all infants, plasma concentrations of free dopamine were measured 1, 2 and 3 h after the first administration. Heart rate and systolic blood pressure were examined before and at the same time as the first administration. In seven infants, the 24 h urinary output and urinary excretion of electrolytes and creatinine before and during docarpamine were measured. Peak plasma concentration of free dopamine (ng/mL) was achieved after 1 or 2 h of administration, 0-163.1 (37.9 +/- 47.2) and 0-105.0 (37.8 +/- 39.3), respectively. The concentration had decreased rapidly by 3 h to 0-34.2 (12.4 +/- 11.0). Both heart rate (b.p.m.) and blood pressure (mmHg) tended to increase from 120-154 (140 +/- 15) and 56-90 (76 +/- 11) to a peak of 124-162 (148 +/- 14) and 70-92 (79 +/- 8), respectively (P = 0.197, P = 0.289). There were no significant changes in urinary output or excreta. Oral docarpamine of 15-20 mg/kg per dose can achieve plasma free concentrations of dopamine that increase heart rate and systolic blood pressure.