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Titolo:
Erythromycin increases plasma concentrations of alpha-dihydroergocryptine in humans
Autore:
de Mey, C; Althaus, M; Ezan, E; Retzow, A;
Indirizzi:
ACPS, D-55252 Mainz, Germany ACPS Mainz Germany D-55252ACPS, D-55252 Mainz, Germany Desitin Arzneimittel GmbH, Hamburg, Germany Desitin Arzneimittel GmbH Hamburg Germany mittel GmbH, Hamburg, Germany Serv Pharmacol & Immunol, Gif Sur Yvette, France Serv Pharmacol & ImmunolGif Sur Yvette France , Gif Sur Yvette, France Serv Pharmacol & Immunol, Reinfeld, France Serv Pharmacol & Immunol Reinfeld France ol & Immunol, Reinfeld, France
Titolo Testata:
CLINICAL PHARMACOLOGY & THERAPEUTICS
fascicolo: 2, volume: 70, anno: 2001,
pagine: 142 - 148
SICI:
0009-9236(200108)70:2<142:EIPCOA>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
P-GLYCOPROTEIN; DRUG-INTERACTIONS; DOUBLE-BLIND; BROMOCRIPTINE; BIOAVAILABILITY; BIOEQUIVALENCE; MULTICENTER; INHIBITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: de Mey, C ACPS, Philippsring 11, D-55252 Mainz, Germany ACPS Philippsring 11 Mainz Germany D-55252 55252 Mainz, Germany
Citazione:
C. de Mey et al., "Erythromycin increases plasma concentrations of alpha-dihydroergocryptine in humans", CLIN PHARM, 70(2), 2001, pp. 142-148

Abstract

Objective. Our objective was to investigate the potential for relevant pharmacotherapeutic interaction between cytochrome P4503A4 (CYP3A4)-inhibitingagents such as erythromycin and the dopamine agonist alpha -dihydroergocryptine (DHEC). Methods. The study was carried out as a single-center, controlled, nonblinded, 2-way crossover clinical trial with randomly allocated period-balancedsequences investigating two treatments of a single oral dose of 10 mg DHEC(on the morning of day 1), once administered alone (reference), once alongwith a 4-day treatment (days -2 to 1) of 500 mg erythromycin 3 times daily. Periods were separated by a washout of at least 14 days. Nine healthy white male volunteers, 22 to 42 years old, with a body weight range of 58 to 90 kg (body mass index, 20.2-25.1 kg (.) m(-2)) began the study. One subjectdiscontinued prematurely, and 8 concluded the study in accordance with thestudy protocol. Results. The plasma and urinary pharmacokinetics of DHEC and its metabolites were characterized by a large variability Concomitant treatment with erythromycin led to respective increases of 9.5 (95% confidence interval [CI],6.5 to 13.9) and 16.5 (95% CI, 8.7 to 31.5) times the maximum observed plasma drug concentration and the a-rea under the time course of the plasma concentrations up to the last quantifiable concentration after dosing of unchanged DHEC (determined by radioimmunoassay). The 24-hour urinary excretion was on average 11 times larger (95% CI, 5.9 to 20.7). Qualitatively similarfindings were recorded for the total of DHEC plus metabolites (as determined by enzyme immunoassay). Conclusions. The concomitant use of erythromycin or similarly CYP3A4-inhibiting agents along, vith direct dopaminergic agonists such as the ergoline DHEC may cause a clinically relevant increase in pharmacokinetic; exposure,which may induce exaggerated dopaminergic effects.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 10:56:42