Evaluation of flurbiprofen urinary ratios as in vivo indices for CYP2C9 activity.

Evaluation of flurbiprofen urinary ratios as in vivo indices for CYP2C9 activity. Research Abstract Details 

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Evaluation of flurbiprofen urinary ratios as in vivo indices for CYP2C9 activity. Abstract Text:

N K Zgheib,R F Frye,T S Tracy,M Romkes,R A Branch,

AIMS: We investigated flurbiprofen pharmacokinetics in 12 volunteers to develop a phenotypic trait measure that correlates with the fractional clearance to 4'-hydroxyflurbiprofen. The effect of the CYP2C9 inhibitor fluconazole on flurbiprofen metabolism was also evaluated. METHODS: Flurbiprofen pharmacokinetics were evaluated before and after the first and seventh doses of fluconazole. The urinary recovery ratio was calculated as FLRR = 4'-OHF/[4'-OHF + F(tot)] and the urinary metabolic ratio was calculated as FLMR = 4'-OHF/F(tot), where 4'-OHF and F(tot) represent total (conjugated and unconjugated) amounts recovered in urine. RESULTS: There was a statistically significant relationship between the 4'-OHF formation clearance (4OHCLf) and both the 8-h FLRR and the 8-h FLMR with and without administration of fluconazole. The flurbiprofen apparent oral clearance (CL/F) was decreased by 53% [90% confidence interval (CI) -58, -48] and 64% (90% CI -69, -59), respectively, after administration of one and seven doses of fluconazole when compared with administration of flurbiprofen alone; similarly, the 4OHCLf decreased by 69% (90% CI -74, -64) and 78% (90% CI -83, -73), the 8-h FLRR decreased by 35% (90% CI -41, -29) and 40% (90% CI -46, -35) and the 8-h FLMR decreased by 61% (90% CI -65, -58) and 67% (90% CI -70, -63). The magnitude of decrease in CL/F and 4OHCLf was greater after seven doses compared with after one dose of fluconazole (P < 0.005). CONCLUSIONS: This study provides strong evidence that both the 8-h FLRR and the 8-h FLMR are suitable phenotypic indices for CYP2C9 activity.

Evaluation of flurbiprofen urinary ratios as in vivo indices for CYP2C9 activity. Publishing Authors By Initials

NK Zgheib,RF Frye,TS Tracy,M Romkes,RA Branch,

For similar genetic phenomena: phenotype research abstracts see: genetic phenomena: phenotype research

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Evaluation of flurbiprofen urinary ratios as in vivo indices for CYP2C9 activity. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: British journal of clinical pharmacology

VOLUME: 63

Page Numbers: 477-87

Journal Abbreviation:

ISSN: 0306-5251

DAY: 19

MONTH: 10

YEAR: 2006

Evaluation of flurbiprofen urinary ratios as in vivo indices for CYP2C9 activity. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503323

Evaluation of flurbiprofen urinary ratios as in vivo indices for CYP2C9 activity. Keywords Mesh Terms:

KEYWORDS: Phenotype

MESH TERMS: urine

Chemical & Substance for Abstract: Evaluation of flurbiprofen urinary ratios as in vivo indices for CYP2C9 activity. Information

Substance Name: Cytochrome P-450 Enzyme System

Registry Number: 9035-51-2

Grant and Affiliation Information for Evaluation of flurbiprofen urinary ratios as in vivo indices for CYP2C9 activity.

AFFILIATION: Center for Clinical Pharmacology, Department of Medicine, University of Pittsburg, Pittsburgh, PA 15219-3138, USA.

Country: England

AGENCY: United States NCRR

GRANT: M01 RR00056

ACRONYM: RR

MEDLINETA: Br J Clin Pharmacol

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