Related Experiment Videos
Diphenylhydantoin elimination kinetics in overdosed children
Clinical Pharmacology and Therapeutics
|April 1, 1975
Summary
Diphenylhydantoin (DPH) overdose in children shows altered pharmacokinetics. Children exhibit lower K-M and higher Vmax values, influencing toxicity onset and HPPH excretion.
Area of Science:
- Pharmacology
- Clinical Toxicology
- Pediatric Pharmacokinetics
Background:
- Diphenylhydantoin (DPH) is an anticonvulsant medication with a narrow therapeutic index.
- Overdose cases in children necessitate understanding DPH's pharmacokinetic profile.
- Previous studies on DPH pharmacokinetics have primarily focused on adult populations.
Purpose of the Study:
- To investigate the pharmacokinetic parameters of Diphenylhydantoin (DPH) elimination in pediatric patients experiencing overdose.
- To compare the in vivo Michaelis-Menten constants (K-M and Vmax) in children with those reported for adult subjects.
- To explore the relationship between DPH serum concentrations, metabolic excretion, and the onset of toxicity in children.
Main Methods:
- Serum and urine samples were collected from four children with DPH overdose (serum concentrations 44-76 mg/l).
- Assays were performed for DPH in serum and for DPH and its metabolite 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH) in urine.
- Simultaneous computer nonlinear regression analysis using a one-compartment pharmacokinetic model was applied to the collected data.
Main Results:
- Computed Vmax values were generally higher and K-M values lower in children compared to adults.
- Higher Vmax values correlated with increased urinary excretion rates of HPPH.
- HPPH excretion rates remained relatively constant at high DPH serum levels, with evidence of a diurnal rhythm.
- The onset of DPH toxicity was linked to the rate of DPH administration exceeding the calculated Vmax.
Conclusions:
- Pediatric patients exhibit distinct DPH pharmacokinetic parameters compared to adults, characterized by potentially faster elimination at high concentrations.
- Understanding these pediatric-specific Vmax and K-M values is crucial for managing DPH overdose and predicting toxicity.
- The metabolic pathway, indicated by HPPH excretion, plays a significant role in DPH clearance, even during overdose scenarios.