title: Toxicodynetics in nordiazepam and oxazepam overdoses.
abstract: OBJECTIVE
  Toxicodynetics aims at defining the time-course of major clinical events in drug overdose. We report the toxicodynetics in mono-intoxications with oxazepam and nordiazepam.
  
  
  METHODS
  Cases of oxazepam or nordiazepam overdoses collected at the Paris poison control centre from 1999 to 2014 on the basis of self-report. A particular attention was paid to eliminate the concomitant alcohol or psychotropic co-ingestions. The toxicodynetic parameters were assessed as previously described. Results are expressed using 10-90 percentiles. In adults, the dose was normalized (TI, toxic Index) by dividing the supposed ingested dose by the maximal recommended dose.
  
  
  RESULTS
  Two hundred and fifty-one and 74 cases of oxazepam and nordiazepam poisonings were included, respectively. The Emax for oxazepam and nordiazepam were sleepiness or obtundation in 106 and 36 cases, respectively. Coma was used to qualify only one oxazepam overdose. The median delay in onset of the Emax was 1.5h (0.33-15) in nordiazepam and 4h (0.5-15) in oxazepam overdose. In both overdoses, the onset of Emax occurred on an "on-off" mode. In adults, the greatest TIs in nordiazepam and oxazepam overdoses were 45 and 26.7, respectively. The TI in the oxazepam-induced coma was 26.7, the largest dose.
  
  
  CONCLUSIONS
  Data collected in PCC allow determining a number of toxicodynetic parameters. Toxicodynetics showed that nordiazepam is not a cause of coma even in large overdose while oxazepam causes coma only at a very high dose. Deep coma in nordiazepam overdose whatever the dose and deep coma in overdose with oxazepam involving TI less than 20 result from unrecognized drug-drug interaction.
authors.affiliation: UMR 8257 cognitive action group, Paris Descartes university, 45, rue des Saints-Pères, 75270 Paris cedex 06, France; Paris poison control centre, hôpital Fernand-Widal, 200, rue du Faubourg-Saint-Denis, 75010 Paris, France. Electronic address: lynnsacre@hotmail.com.
authors.forename: L
authors.initials: L
authors.lastname: Sacre
authors.affiliation: UMR 8257 cognitive action group, Paris Descartes university, 45, rue des Saints-Pères, 75270 Paris cedex 06, France; Paris poison control centre, hôpital Fernand-Widal, 200, rue du Faubourg-Saint-Denis, 75010 Paris, France. Electronic address: mohamed-ali.safia@live.fr.
authors.forename: S M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: Paris poison control centre, hôpital Fernand-Widal, 200, rue du Faubourg-Saint-Denis, 75010 Paris, France. Electronic address: antoine.villa@aphp.fr.
authors.forename: A
authors.initials: A
authors.lastname: Villa
authors.affiliation: Department of anesthesiology-intensive care, hôpital Necker, 149, rue de Sèvres, 75015 Paris, France. Electronic address: romain.jouffroy@aphp.fr.
authors.forename: R
authors.initials: R
authors.lastname: Jouffroy
authors.affiliation: Department of anesthesiology-intensive care, hôpital Necker, 149, rue de Sèvres, 75015 Paris, France. Electronic address: jean-herle.raphalen@aphp.fr.
authors.forename: J-H
authors.initials: JH
authors.lastname: Raphalen
authors.affiliation: Paris poison control centre, hôpital Fernand-Widal, 200, rue du Faubourg-Saint-Denis, 75010 Paris, France; Paris Diderot university, Paris, France. Electronic address: robert.garnier@aphp.fr.
authors.forename: R
authors.initials: R
authors.lastname: Garnier
authors.affiliation: UMR 8257 cognitive action group, Paris Descartes university, 45, rue des Saints-Pères, 75270 Paris cedex 06, France; Paris poison control centre, hôpital Fernand-Widal, 200, rue du Faubourg-Saint-Denis, 75010 Paris, France; Department of anesthesiology-intensive care, hôpital Necker, 149, rue de Sèvres, 75015 Paris, France; Paris Diderot university, Paris, France. Electronic address: baud.frederic@wanadoo.fr.
authors.forename: F J
authors.initials: FJ
authors.lastname: Baud
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D062787:Drug Overdose / Q000378:metabolism*; D000431:Ethanol / Q000009:adverse effects; D005260:Female; D018757:GABA Modulators / Q000009:adverse effects* / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D003708:Nordazepam / Q000009:adverse effects* / Q000493:pharmacokinetics*; D010076:Oxazepam / Q000009:adverse effects* / Q000493:pharmacokinetics*; D012189:Retrospective Studies; D066007:Toxicokinetics; D055815:Young Adult
chemical_list: D002492:Central Nervous System Depressants; D018757:GABA Modulators; D000431:Ethanol; D003708:Nordazepam; D010076:Oxazepam
keywords: Centre antipoison; Intoxication; Nordazépam; Nordiazepam; Overdoses; Oxazepam; Oxazépam; Pharmacovigilance; Poison control centre; Toxicodynetics; Toxicodynétique