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Titolo:
Studies on the mechanism of a fatal clarithromycin-pimozide interaction ina patient with Tourette syndrome
Autore:
Flockhart, DA; Drici, MD; Kerbusch, T; Soukhova, N; Richard, E; Pearle, PL; Mahal, SK; Babb, VJ;
Indirizzi:
Georgetown Univ, Med Ctr, Div Clin Pharmacol, Dept Med, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 ept Med, Washington, DC 20007 USA Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 armacol, Washington, DC 20007 USA Washington Hosp Ctr, Dept Neurol, Washington, DC 20010 USA Washington HospCtr Washington DC USA 20010 rol, Washington, DC 20010 USA US FDA, Off Epidemiol & Biostat, Div Pharmacovigilance & Epidemiol, Rockville, MD 20857 USA US FDA Rockville MD USA 20857 ilance & Epidemiol, Rockville, MD 20857 USA
Titolo Testata:
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
fascicolo: 3, volume: 20, anno: 2000,
pagine: 317 - 324
SICI:
0271-0749(200006)20:3<317:SOTMOA>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
SYSTEMIC ANTIMYCOTICS KETOCONAZOLE; TORSADES-DE-POINTES; CYTOCHROME-P450 ISOFORMS; HYDROXYLATION PHENOTYPE; PLASMA-LEVELS; ERYTHROMYCIN; PHARMACOKINETICS; TERFENADINE; ITRACONAZOLE; HALOPERIDOL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Flockhart, DA Georgetown Univ, Med Ctr, Div Clin Pharmacol, Dept Med, RoomNE 403,Med Dent Bldg,3900 Reservoir Rd, Washington, DC 20007 USA Georgetown Univ Room NE 403,Med Dent Bldg,3900 Reservoir Rd Washington DC USA 20007
Citazione:
D.A. Flockhart et al., "Studies on the mechanism of a fatal clarithromycin-pimozide interaction ina patient with Tourette syndrome", J CL PSYCH, 20(3), 2000, pp. 317-324

Abstract

The authors report in detail the case of a 27-year-old man who experiencedsudden cardiac death 2 days after coprescription of the neuroleptic pimozide and the macrolide antibiotic clarithromycin after the documentation of aprolonged QT interval. To determine the prevalence of this interaction, the authors referred to the Spontaneous Reporting System of the Food and DrugAdministration and identified one similar case in which clarithromycin wascoprescribed with pimozide and sudden cardiac death occurred shortly thereafter. In addition, the search identified 39 cases of cardiac arrhythmia associated with pimozide, 11 with pimozide alone, and 6 with clarithromycin alone, 1 of which had a positive rechallenge. The mechanism of the interaction between clarithromycin and pimozide seems to involve the inhibition of the hepatic metabolism of pimozide by the macrolide. The authors demonstrated that clarithromycin is able to inhibit the metabolism of pimozide in human liver microsomal preparations (K-i = 7.65 +/- 1.18 mu M) and that pimozide, but not clarithromycin or its primary metabolite, is able to prolong theelectrocardiac QT interval in a dose-dependent manner in the isolated perfused rabbit heart. The increase was 9.6 +/- 1.1% in male hearts (N = 5) and13.4 +/- 1.2% in female hearts (N = 4) (p < 0.05).

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 19:47:12