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Titolo:
FEATURES AND TOXICOKINETICS OF CLOZAPINE IN OVERDOSE
Autore:
REITH D; MONTELEONE JPR; WHYTE IM; EBELLING W; HOLFORD NHG; CARTER GL;
Indirizzi:
NEWCASTLE MATER MISERICORDIAE HOSP,DEPT CLIN TOXICOL & PHARMACOL,LOCKED BAG 7 HUNTER NSW 2310 AUSTRALIA NEWCASTLE MATER MISERICORDIAE HOSP,DEPT CLIN TOXICOL & PHARMACOL HUNTER NSW 2310 AUSTRALIA UNIV AUCKLAND,SCH MED,DEPT PHARMACOL & CLIN PHARMACOL AUCKLAND NEW ZEALAND ROYAL CHILDRENS HOSP HERSTON QLD AUSTRALIA HUNTER AREA PATHOL SERV,DIV CLIN CHEM NEWCASTLE NSW AUSTRALIA NEWCASTLE MATER MISERICORDIAE HOSP,DEPT LIAISON PSYCHIAT NEWCASTLE NSW AUSTRALIA
Titolo Testata:
Therapeutic drug monitoring
fascicolo: 1, volume: 20, anno: 1998,
pagine: 92 - 97
SICI:
0163-4356(1998)20:1<92:FATOCI>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
DRUGS;
Keywords:
CLOZAPINE; NORCLOZAPINE; OVERDOSE; POISONING; MKMODEL; MODELING; TOXICOKINETICS; CASE SERIES; INCIDENCE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
26
Recensione:
Indirizzi per estratti:
Citazione:
D. Reith et al., "FEATURES AND TOXICOKINETICS OF CLOZAPINE IN OVERDOSE", Therapeutic drug monitoring, 20(1), 1998, pp. 92-97

Abstract

One hundred patients were commenced on clozapine in the Hunter regionof Australia from July 1993 to September 1995. Of these, one ingestedclozapine as a self-poisoning on two occasions. Over the same period,there were four other self-poisonings with clozapine in the region. Another case from a different region is described. The cases were identified from the Hunter Area Toxicology Service Database and regional psychiatric hospitals. The severity of the poisoning is related to priorexposure and tolerance. Marked sedation at relatively low doses occurred in the absence of prior exposure. No reversible electrocardiographic changes or biochemical abnormalities were demonstrated. Anticholinergic effects were minimal, All seven cases made full recovery. A high-pressure liquid chromatography (HPLC) method for assaying clozapine and its major metabolite, norclozapine, in plasma is described. Approximate retention times were norclozapine, 3.8 minutes; clozapine, 5 minutes; and propyl-norclozapine, 7 minutes. The lower limit of analysis for this assay was 20 ng/ml for clozapine and the metabolite, Using the HPLC assay, serial clozapine and norclozapine plasma concentrations were measured in three of these cases of clozapine self poisoning. Toxicokinetic modeling was conducted by simultaneous analysis of clozapine and norclozapine observations. A two-compartment model with a metabolite compartment attached to the central compartment was used. Clozapinemetabolism to norclozapine was best described by linear elimination of norclozapine and nonlinear norclozapine formation. The K-m (1918 +/-2093 mu g/l) relative to observed concentration (3396 +/- 962 mu g/l)suggests that norclozapine formation was saturated at the time of thefirst observation.

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Documento generato il 19/01/20 alle ore 06:05:16