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The pharmacokinetics of theophylline in an infant with hepatic failure
Insights
Hereditary tyrosinemia in an infant led to liver failure, significantly slowing theophylline metabolism and prolonging its half-life. This case highlights impaired drug clearance in infants with hepatic dysfunction.
Area of Science:
- Pharmacology
- Hepatology
- Pediatrics
Background:
- Hereditary tyrosinemia is a rare genetic disorder that can lead to severe liver dysfunction.
- Theophylline is a medication commonly used for respiratory conditions, and its metabolism can be affected by liver function.
Observation:
- A 6 1/2-month-old infant with hepatic failure due to hereditary tyrosinemia exhibited significantly reduced theophylline clearance (0.016 L/kg/h) and a prolonged serum half-life (18.0 h).
- Urine analysis detected theophylline and caffeine but not key metabolites like 1-methyluric acid, 1,3-dimethyluric acid, or 3-methylxanthine 48 hours post-dose.
Findings:
- The infant's theophylline disposition was markedly impaired, consistent with severe hepatic dysfunction.
- The absence of specific theophylline metabolites suggests a significant disruption in the metabolic pathways within the compromised liver.
Implications:
- This case underscores the critical impact of liver dysfunction on drug metabolism in infants.
- Understanding altered drug disposition in pediatric liver disease is crucial for safe and effective pharmacotherapy.
- Further research is needed to elucidate the specific metabolic deficits in hereditary tyrosinemia affecting drug clearance.
Abstract:
In a 6 1/2-month-old infant with hepatic failure secondary to hereditary tyrosinemia, the theophylline clearance rate of 0.016 liter/kg/h was reduced for age and the serum half-life was prolonged to 18.0 h. Theophylline, 3.4 micrograms/ml, and caffeine, 2.2 micrograms/ml, were identified in a urine sample obtained 48 h after the test dose of theophylline, but no 1-methyluric acid, 1,3-dimethyluric acid or 3-methylxanthine were detected. This is the first infant with liver dysfunction and impaired theophylline disposition to be reported.