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Titolo:
Influence of stereoselective pharmacokinetics in the development and predictability of an IVIVC for the enantiomers of metoprolol tartrate
Autore:
Sirisuth, N; Eddington, ND;
Indirizzi:
Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet BiopharmaceutLab,AHB, Baltimore, MD 21201 USA Univ Maryland Baltimore MD USA 21201 ceutLab,AHB, Baltimore, MD 21201 USA
Titolo Testata:
PHARMACEUTICAL RESEARCH
fascicolo: 8, volume: 17, anno: 2000,
pagine: 1019 - 1025
SICI:
0724-8741(200008)17:8<1019:IOSPIT>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
DRUG ENANTIOMERS; RELEASE; FORMULATIONS;
Keywords:
IVIVC; racemate; enantiomers; metoprolol; pharmacokinetics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
15
Recensione:
Indirizzi per estratti:
Indirizzo: Eddington, ND Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, PharmacokinetBiopharmaceutLab,AHB, 100 Penn St, Baltimore, MD 21201 USA Univ Maryland 100 Penn St Baltimore MD USA 21201 D 21201 USA
Citazione:
N. Sirisuth e N.D. Eddington, "Influence of stereoselective pharmacokinetics in the development and predictability of an IVIVC for the enantiomers of metoprolol tartrate", PHARM RES, 17(8), 2000, pp. 1019-1025

Abstract

Purpose. To investigate the ability of an IVIVC developed with a racemate drug as well as each enantiomer in predicting the in vivo enantiomer drug performance. Methods. Dissolution of metoprolol extended release tablets with differentrelease characteristics (e.g., fast (F), moderate (M), and slow (S)) was performed using USP Apparatus I, pH 1.2, 50 rpm. Metoprolol racemate tablets(S, M, and F, 100 mg) and 50 mg oral solution were administered to healthyvolunteers, blood samples were collected over 24 (solution) and 48 (tablet) hours and assayed. IVIVC models developed were: (1) Racemate-fraction of drug dissolved (FRD) vs Racemate-fraction of drug absorbed (FRA), (2) R-FRDvs R-FRA, and (3) S-FRD vs S-FRA for combinations of formulations (S/M/F, S/M, S/F, and M/F). Enantiomer Cmax and AUC prediction errors (PEs) were estimated for model evaluation after convolution of in vivo release rates. Results. The R-IVIVC and S-IVIVC accurately predicted the R- and S-metoprolol pharmacokinetic profiles, respectively. The averaged prediction errors (PE) for the enantiomer Cmax and AUC were less than 10% for S/M/F, M/F, andSIF IVIVC models. Racemate-IVIVC (M/F) was able to predict S-enantiomer with an average %PE of 2.52 for S-Cmax and 4.3 for S-AUC. However, the racemate-IVIVC was unable to predict the R-enantiomer pharmacokinetic profile. Conclusions. Metoprolol racemate data cannot be used to accurately predictR-enantiomer drug concentrations. However, the racemate data was predictive of the active stereoisomer.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 13:30:50