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[Pharmacokinetics of diphemanil methylsulfate in infants]
1Centre d'urgence et de diagnostic rapide, hôpital des Enfants-Malades, Paris, France.
Insights
Diphemanil methylsulfate pharmacokinetic parameters were determined in infants for the first time. The drug
Area of Science:
- Pharmacology
- Pediatrics
- Clinical Pharmacy
Background:
- Diphemanil methylsulfate is an atropine-like medication used for infant vagal bradycardia.
- Adult pharmacokinetic data exist, but infant data are lacking.
- This study investigates diphemanil methylsulfate pharmacokinetics in infants.
Purpose of the Study:
- To determine the pharmacokinetic parameters of diphemanil methylsulfate in infants.
- To compare infant parameters with adult data.
- To inform appropriate dosing and administration intervals for infants.
Main Methods:
- Six infants (10-109 days old) received a single oral dose of 3 mg/kg diphemanil methylsulfate.
- Blood samples were collected serially for 24 hours post-dose.
- Plasma drug concentrations were measured using gas-exchange chromatography.
Main Results:
- Peak plasma concentrations occurred at a mean of 3.9 hours in older infants.
- The drug's half-life was 8.6 hours, decreasing with age, but longer (17.2 hours) in a younger infant.
- Renal clearance was high, indicating efficient excretion.
Conclusions:
- The pharmacokinetic profile supports an 8-hour dosing interval for diphemanil methylsulfate in infants.
- This dosing schedule offers improved convenience for infants and caregivers.
- High renal clearance suggests both glomerular filtration and tubular secretion are involved in drug excretion.
Background:
Diphemanil methylsulfate is an atropin-like drug used in some infants suffering from vagal bradycardia. Its pharmacokinetic parameters are known for adults but not for infants. The report describes these parameters in six infants.
Population And Methods:
Five infants aged 35 to 109 days (mean: 62 +/- 28) and weighing 3.5 to 5.3 kg (mean: 4.3) were included in the study with the formal consent of their parents. All suffered from vagal hyperreactivity. The sixth younger full-term infant was aged 10 days and weighed 4 kg. They were given a single dose (3 mg/kg) of diphemanil methylsulfate orally, after a minimal fast of 4 hours. Blood samples were collected at T0 and 3, 6, 8, 12 and 24 hours after administration. Urines were also collected from 1 hour before drug administration to 24 hours after. Plasma concentrations of diphemanil methylsulfate were measured by gas-exchange chromatography.
Results:
The peak plasma concentration in the five infants occurred at 3.9 +/- 2.3 hours (range: 2.9-8 hours). Half-life was 8.6 +/- 2.4 hours and tended to decrease with age. All the other parameters were identical to those found in adults. The peak plasma concentration occurred in the sixth younger infant at 2.9 hours, with a half-life of 17.2 hours. Renal clearance was high (0.3 l/h/kg).
Conclusion:
The relatively long half-life of diphemanil methylsulfate allows this drug to be given every 8 hours. This longer interval is more comfortable for the patients and their parents. The high renal clearance suggests that this drug is excreted by both glomerular filtration and tubular secretion.