Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Effect of naproxen co-administration on valproate disposition
Autore:
Addison, RS; Parker-Scott, SL; Hooper, WD; Eadie, MJ; Dickinson, RG;
Indirizzi:
Univ Queensland, Royal Brisbane Hosp, Ctr Studies Drug Disposit, Brisbane,Qld 4029, Australia Univ Queensland Brisbane Qld Australia 4029 Brisbane,Qld 4029, Australia
Titolo Testata:
BIOPHARMACEUTICS & DRUG DISPOSITION
fascicolo: 6, volume: 21, anno: 2000,
pagine: 235 - 242
SICI:
0142-2782(200009)21:6<235:EONCOV>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLASMA-PROTEIN BINDING; QUANTITATIVE-DETERMINATION; BETA-OXIDATION; ACID; METABOLITES; HUMANS; SERUM; GLUCURONIDATION; CHROMATOGRAPHY; CARBAMAZEPINE;
Keywords:
drug interaction; glucuronidation; naproxen; beta-oxidation; protein binding; valproic acid;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Addison, RS Univ Queensland, Royal Brisbane Hosp, Ctr Studies Drug Disposit, Clin Sci Bldg, Brisbane, Qld 4029, Australia Univ Queensland Clin Sci Bldg Brisbane Qld Australia 4029 alia
Citazione:
R.S. Addison et al., "Effect of naproxen co-administration on valproate disposition", BIOPHARM DR, 21(6), 2000, pp. 235-242

Abstract

The effects of co-administration of the antiepileptic agent valproic acid (VPA) and the non-steroidal anti-inflammatory drug naproxen (NAP) on their relative dispositions (particularly with respect to glucuronidation) were investigated in human volunteers. Seven healthy males received each drug alone and then in combination (orally twice daily for seven days, 500 mg sodium VPA, 500 mg NAP). On day 7 of each dosing phase, serial plasma and 24 h urine samples were collected for analysis. Go-administration of NAP resultedin significant increases (about 20%, p < 0.05) in the apparent plasma clearance of total VPA and in the unbound fraction of VPA in plasma, with the apparent plasma clearance of unbound VPA being unchanged. There were associated increases in the formation clearances to urinary VFA-glucuronide and 3-oxo-VPA, though these were relatively greater for the glucuronidation pathway land remained significant when formation clearances were calculated using the unbound fraction of drug in plasma). The data thus point to a shift towards glucuronidation as a result of the NAP-induced increase in the unbound fraction of VPA in plasma. By contrast, VPA coadministration caused a decrease (of about 10%, p < 0.05) in the apparent plasma clearance of total NAP. Taken in hand with in vitro results showing a VPA-induced displacement (of about 40%) of NAP from plasma protein binding sites, the data strongly support a role for diminished glucuronidation of NAP and its desmethyl metabolite in the presence of co-administered VPA. Copyright (C) 2000 John Wiley & Sons, Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 12:52:59