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Titolo:
PHARMACOKINETIC-PHARMACODYNAMIC INTERACTION BETWEEN THE COMT INHIBITOR TOLCAPONE AND SINGLE-DOSE LEVODOPA
Autore:
DINGEMANSE J; JORGA K; ZURCHER G; SCHMITT M; SEDEK G; DAPRADA M; VANBRUMMELEN P;
Indirizzi:
F HOFFMANN LA ROCHE & CO LTD,DEPT CLIN PHARMACOL CH-4002 BASEL SWITZERLAND F HOFFMANN LA ROCHE & CO LTD,DEPT PRECLIN RES CH-4002 BASEL SWITZERLAND
Titolo Testata:
British journal of clinical pharmacology
fascicolo: 3, volume: 40, anno: 1995,
pagine: 253 - 262
SICI:
0306-5251(1995)40:3<253:PIBTCI>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
CATECHOL-O-METHYLTRANSFERASE; PARKINSONS-DISEASE; METHYL TRANSFERASE; HEALTHY-VOLUNTEERS; DRUG-THERAPY; METABOLISM; DOPA; RO-40-7592; PLASMA; RAT;
Keywords:
TOLCAPONE; LEVODOPA; COMT INHIBITION; ERYTHROCYTES; PHARMACOKINETICS; PHARMACODYNAMICS; CONCENTRATION-EFFECT RELATIONSHIP; MODELING; PARKINSONS DISEASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
J. Dingemanse et al., "PHARMACOKINETIC-PHARMACODYNAMIC INTERACTION BETWEEN THE COMT INHIBITOR TOLCAPONE AND SINGLE-DOSE LEVODOPA", British journal of clinical pharmacology, 40(3), 1995, pp. 253-262

Abstract

1 Single oral doses of the catechol-O-methyltransferase (COMT) inhibitor tolcapone (10-800 mg) or placebo were administered simultaneously with a dose of levodopa/benserazide 100/25 mg to seven sequential groups of six healthy male subjects in a two-way crossover study. 2 Plasmaconcentrations of tolcapone, its metabolite 3-O-methyltolcapone, levodopa and 3-O-methyldopa (3-OMD) were determined in conjunction with COMT activity in erythrocytes. 3 The drug combination was well toleratedat all dose levels and there were no signs indicative of an increase in dopaminergic stimulation. 4 Tolcapone caused a rapid and reversibleinhibition of COMT activity in erythrocytes in parallel with a dose-dependent decrease in the formation of 3-OMD. Tolcapone increased the area under the concentration-time curve and elimination half-life of levodopa. The maximum effects were obtained at a dose of about 200 mg when both parameters increased approximately twofold. The drug had no influence on the maximum concentration of levodopa. 5 Tolcapone was rapidly absorbed and eliminated with, on average, a t(max) of 1.5 h and a t1/2 of 2.3 h. The drug showed dose-proportional pharmacokinetics, in contrast to 3-O-methyltolcapone whose formation was relatively decreased at higher doses. 6 Plasma concentrations of tolcapone correlated with inhibition of COMT activity in erythrocytes and suppression of 3-OMD levels, but not with changes in levodopa pharmacokinetics.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/09/20 alle ore 11:50:05