title: [Pharmacokinetics of diphemanil methylsulfate in infants].
abstract: 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre d'urgence et de diagnostic rapide, hôpital des Enfants-Malades, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Chéron
authors.forename: A M
authors.initials: AM
authors.lastname: Vidal
authors.forename: E
authors.initials: E
authors.lastname: Rey
authors.forename: G
authors.initials: G
authors.lastname: Pons
authors.forename: P
authors.initials: P
authors.lastname: d'Athis
authors.forename: G
authors.initials: G
authors.lastname: Olive
mesh_terms: D000367:Age Factors; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D008297:Male; D010276:Parasympatholytics / Q000493:pharmacokinetics* / Q000494:pharmacology; D010880:Piperidines / Q000493:pharmacokinetics* / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology
chemical_list: D010276:Parasympatholytics; D010880:Piperidines; C028209:diphemanil methylsulfate
vernacular_title: Pharmacocinétique du diphémanil méthylsulfate chez le nourrisson.