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Titolo:
SATURABLE ELIMINATION AND SATURABLE PROTEIN-BINDING ACCOUNT FOR FLAVONE ACETIC-ACID PHARMACOKINETICS
Autore:
RELLING MV; EVANS RR; GROOM S; CROM WR; PRATT CB;
Indirizzi:
ST JUDE CHILDRENS HOSP,DIV PHARMACEUT,332 N LAUDERDALE MEMPHIS TN 38101 UNIV TENNESSEE MEMPHIS TN 00000
Titolo Testata:
Journal of pharmacokinetics and biopharmaceutics
fascicolo: 6, volume: 21, anno: 1993,
pagine: 639 - 651
SICI:
0090-466X(1993)21:6<639:SEASPA>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHASE-I; SOLID TUMORS; DISOPYRAMIDE; NSC-347512; METABOLISM; KINETICS; DRUGS;
Keywords:
PLASMA PROTEIN BINDING; MICHAELIS-MENTEN ELIMINATION; PHARMACOKINETICS; FLAVONE ACETIC ACID;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
21
Recensione:
Indirizzi per estratti:
Citazione:
M.V. Relling et al., "SATURABLE ELIMINATION AND SATURABLE PROTEIN-BINDING ACCOUNT FOR FLAVONE ACETIC-ACID PHARMACOKINETICS", Journal of pharmacokinetics and biopharmaceutics, 21(6), 1993, pp. 639-651

Abstract

Flavone acetic acid (FAA) is an antineoplastic agent that has undergone extensive study in Phase I trials Concentration-dependent plasma protein binding has been demonstrated in vitro at concentrations of total drug that are achieved in vivo. Moreover, dose-dependent total systemic clearance has been described when FAA has been administered as a short iv infusion. When administered as a prolonged 24-hr infusion, total FAA (bound plus unbound) plasma pharmacokinetics are well describedwith a first-order two-compartment model. However, measurement of unbound FAA intra- and post-intravenous infusion in eight patients revealed a twofold increase in fraction of FAA unbound in plasma intrainfusion. We attempted to fit pharmacokinetic structural models of varying complexity to the unbound concentrations alone and simultaneously to the unbound arid bound FAA plasma concentrations. The data were adequately described only by a model that incorporated simultaneous saturable plasma protein binding and a Michaelis-Menten process for Elimination. A comparison among models is presented, as well as pharmacokinetic parameter estimates for FAA in children. These clinical data are consistent with predictions of the clearance model in which both saturable protein binding (resulting in a dynamically increasing unbound fraction)and saturable elimination (resulting in gradually decreasing unbound intrinsic clearance) are operative.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 20:30:26