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Titolo:
In-vivo indices of enzyme activity: the effect of renal impairment on the assessment of CYP2D6 activity
Autore:
Rostami-Hodjegan, A; Kroemer, HK; Tucker, GT;
Indirizzi:
Univ Sheffield, Royal Hallamshire Hosp, Div Clin Sci, Sect Mol Pharmacol &Pharmacogenet, Sheffield S10 2JF, S Yorkshire, England Univ Sheffield Sheffield S Yorkshire England S10 2JF S Yorkshire, England Univ Greifswald, Dept Pharmacol, Greifswald, Germany Univ Greifswald Greifswald Germany Dept Pharmacol, Greifswald, Germany
Titolo Testata:
PHARMACOGENETICS
fascicolo: 3, volume: 9, anno: 1999,
pagine: 277 - 286
SICI:
0960-314X(199906)9:3<277:IIOEAT>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEXTROMETHORPHAN N-DEMETHYLATION; OXIDATION POLYMORPHISM; URINARY-EXCRETION; LIVER-MICROSOMES; O-DEMETHYLATION; METABOLISM; HUMANS; METOPROLOL; SPARTEINE; HYDROXYLATION;
Keywords:
drug metabolism; genetic polymorphism; CYP2D6; renal failure;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Tucker, GT Univ Sheffield, Royal Hallamshire Hosp, Div Clin Sci, Sect Mol Pharmacol &Pharmacogenet, Sheffield S10 2JF, S Yorkshire, England Univ Sheffield Sheffield S Yorkshire England S10 2JF , England
Citazione:
A. Rostami-Hodjegan et al., "In-vivo indices of enzyme activity: the effect of renal impairment on the assessment of CYP2D6 activity", PHARMACOGEN, 9(3), 1999, pp. 277-286

Abstract

Urinary drug:metabolite ratios and urinary recoveries of metabolites, havebeen used to assess specific enzyme activity non-invasively in vivo. Theseindices are potentially confounded by the effect of renal function. A recent study of the effects of renal impairment has found discrepancies betweendifferent indices used to mark CYP2D6 activity based on sparteine and dextromethorphan urinary recoveries. We have re-examined these experimental data from a theoretical viewpoint. The results suggest that the dependence of fractional urinary recovery of metabolites on renal function varies with the importance of different elimination routes. Therefore, no consistent behaviour of this index is expected when markers with different pharmacokinetics are used. However, when collecting the urine until full recovery of drug and metabolite, drug:metabolite ratios show the same degree of dependence on renal function regardless of the marker. The application of the analysis to the experimental data indicates that CYP2D6 activity is compromised in parallel with deterioration of renal function. Pharmacogenetics 9:277-286 (C) 1999 Lippincott Williams & Wilkins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 16:00:23