Related Experiment Videos
Kinetics of terbutaline in asthmatic children
Insights
Pediatric asthma patients showed distinct terbutaline pharmacokinetics. Children exhibited shorter drug half-lives and higher clearance rates compared to adults, impacting oral bioavailability.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Clinical Pharmacy
Background:
- Asthma affects millions of children globally, necessitating effective bronchodilator therapy.
- Terbutaline sulfate is a commonly used beta-2 agonist for asthma management.
- Understanding the pharmacokinetic profile of terbutaline in children is crucial for optimizing dosage and efficacy.
Purpose of the Study:
- To characterize the pharmacokinetics of terbutaline sulfate in children with asthma.
- To compare intravenous and oral administration routes in this pediatric population.
- To assess the impact of first-pass metabolism on oral bioavailability.
Main Methods:
- Seven asthmatic children (8-12 years) received intravenous and oral terbutaline sulfate doses one week apart.
- Plasma and urine samples were analyzed for unchanged terbutaline and its conjugates.
- Pharmacokinetic parameters including half-life, clearance, volume of distribution, and bioavailability were calculated.
Main Results:
- The intravenous plasma concentration-time curve exhibited multiexponential decline with a mean terminal half-life of 12.1 hours.
- Mean body clearance was 3.76 mL/min/kg, with a renal clearance of 2.42 mL/min/kg.
- Oral bioavailability was significantly limited (9.5%) due to a mean 70% first-pass elimination, despite 33% absorption.
Conclusions:
- Children with asthma demonstrate shorter terbutaline terminal half-lives and higher weight-corrected clearances than adults.
- Oral terbutaline sulfate in children is subject to substantial first-pass metabolism, leading to low bioavailability.
- These findings suggest potential differences in drug metabolism and elimination pathways in pediatric populations that warrant further investigation.
Abstract:
Seven asthmatic children (8-12 years) were given terbutaline sulphate intravenously (5.5 micrograms/kg) and orally (50 micrograms/kg) one week apart. Unchanged terbutaline was measured in plasma and urine. In urine, conjugates were also assayed. The intravenous plasma concentration-time curve declined in a multiexponential manner. The terminal half-life ranged from 8.8 to 15.8 (mean 12.1) h. Body clearance (mean +/- SD) was 3.76 +/- 0.86, renal clearance 2.42 +/- 0.49 mL/min/kg. The volume of distribution at steady state was 1.57 +/- 0.19 L/kg. The extrapolated recovery of intact terbutaline in urine was 65.4 +/- 6.5% of the dose and the total recovery 80.8 +/- 8.4%. After oral administration, the recovery of intact terbutaline in urine was 6.2 +/- 1.1%. Absorption was on average 33%, but because of a mean first-pass elimination of 70%, bioavailability was 9.5 +/- 2.4%. It seems that children as a group have shorter terminal half-lives than adults and slightly higher weight-corrected clearances.