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Titolo:
Population pharmacokinetic-pharmacodynamic modeling of Filgrastim (r-metHuG-CSF) in healthy volunteers
Autore:
Wang, B; Ludden, TM; Cheung, EN; Schwab, GG; Roskos, LK;
Indirizzi:
Univ Nebraska, Med Ctr, Coll Pharm, Dept Pharmaceut Sci, Omaha, NE 68198 USA Univ Nebraska Omaha NE USA 68198 Dept Pharmaceut Sci, Omaha, NE 68198 USA Amgen Inc, Dept Pharmacokinet & Drug Metab, Thousand Oaks, CA 91320 USA Amgen Inc Thousand Oaks CA USA 91320 g Metab, Thousand Oaks, CA 91320 USA
Titolo Testata:
JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS
fascicolo: 4, volume: 28, anno: 2001,
pagine: 321 - 342
SICI:
1567-567X(200108)28:4<321:PPMOF(>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
COLONY-STIMULATING FACTOR; GRANULOCYTE; CELLS;
Keywords:
Filgrastim; G-CSF; pharmacokinetic-pharmacodynamic modeling; population approach; neutrophil; NONMEM; bisegmental input;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
18
Recensione:
Indirizzi per estratti:
Indirizzo: Ludden, TM GloboMax LLC, 7250 Pkwy Dr, Hanover, MD 21076 USA GloboMax LLC 7250 Pkwy Dr Hanover MD USA 21076 er, MD 21076 USA
Citazione:
B. Wang et al., "Population pharmacokinetic-pharmacodynamic modeling of Filgrastim (r-metHuG-CSF) in healthy volunteers", J PHARMA PH, 28(4), 2001, pp. 321-342

Abstract

The pharmacokinetic-pharmacodynamic (PK-PD) relationship of the granulopoietic effects of Filgrastim in healthy volunteers was characterized via a population approach. Healthy male volunteers were enrolled into a four-way crossover clinical trial. Subjects received four single doses of Filgrastim (375 and 750 mug iv and sc) with an intervening washout period of 7 days. Serum concentrations of Filgrastim were determined using an enzyme-linked immunosorbent assay. Absolute neutrophil count (ANC) was determined. Data analysis was performed using mixed-effects modeling as implemented in the NONMEM software package. The final PKPD model incorporates a two-compartment PK model with bisegmental absorption from the sc site, first-order and saturable elimination pathways, and an indirect PD model. A sigmoidal E-max model for the stimulation of ANC input rate (k(in)) was superior to the conventional E-max model ((x) over bar +/- SE: E-max = 12.7 +/- 1.7; EC50 = 4.72 +/-0.72 ng/ml; Hill = 1.34 +/- 0.19). In addition, a time-variant scaling factor for ANC observations was introduced to account for the early transient depression of ANC after Filgrastim administration. The absolute bioavailability of subcutaneously administered Filgrastim was estimated to be 0.619 +/- 0.058 and 0.717 +/- 0.028 for 375 mug and 750 mug sc doses, respectively. The time profiles of concentration and ANC, as well as the concentration-ANC relationship of Filgrastim in healthy volunteers were well described by the developed population PK-PD model.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/01/20 alle ore 14:52:48